Albumin (Serum Albumin)
Sample for Albumin
- It is done on the serum of the patient.
- Get good serum: Take 3 to 5 ml of blood in the disposable syringe or a vacutainer. Keep the syringe for 15 to 30 minutes at 37 °C and then centrifuge for 2 to 4 minutes to get the clear serum.
- A random sample can be taken.
- Use a freshly prepared serum or store it at four °C, which may be stable for more than 72 hours.
- A fasting sample is preferred.
- Specimens with lipemia or hemolysis should be avoided.
- Avoid prolonged tourniquet. This may increase Albumin and proteins.
- Take into account physical exercise and fever where there is increased filtration.
- Blood samples after the I/V therapy may give low value.
- The drugs which increase the level are anabolic steroids, androgens, corticosteroids, insulin, progesterone, and growth hormone.
- The drugs that can decrease the level are estrogens, hepatotoxic drugs, and oral contraceptives.
Indications for serum albumin
- This test is advised for:
- In liver diseases as a part of a liver panel test.
- Kidney diseases and nephrotic syndrome patients.
- In patients with a severe burn.
- As a part of other tests.
- In a patient suspected of malnutrition.
- In patients where there is a loss from the intestine.
- Patients with cancers, particularly lymphoma and multiple myeloma.
- Albumin is estimated in the third trimester of pregnancy, which may decrease the total protein level.
Pathophysiology of Albumin
- This is the most abundant protein in the blood.
- Around 40% of Albumin is present in the plasma and 60% in the extracellular space. Albumin is the abundant protein in the plasma, constituting 2/3 of total proteins.
- Plasma proteins are separated into three major groups:
- Fibrinogen (4%).
- Globulins (38%).
- Albumin (58%).
- Total serum proteins are a combination of prealbumin, Albumin, and globulins.
- Albumin is a globular protein with a molecular mass of 66.3 kD.
- Albumin consists of one polypeptide chain of 585 amino acids and contains 17 disulfide bonds.
- Albumin is an anion at pH 7.4 with >200 negative charges per molecule.
- It has no carbohydrate side chains but is highly soluble in water due to its high net negative charge at physiologic pH.
- Albumin can not be stored in the parenchymal cells because of a lack of side Carbohydrate chains.
- It accounts for approximately half of the plasma proteins.
- This is the major protein component of most extravascular body fluids like CSF, urine, amniotic fluid, and interstitial fluid.
- The most common method to separate the proteins is electrophoresis. There are five bands named:
- Albumin. It is roughly 60% of the total serum proteins, and it will migrate farthest towards the anode.
- α1 fraction.
- α2 fraction.
- β fraction.
- γ fraction.
Various proteins in the blood, cord blood, and serum:
Type of proteins Cord blood g/dL Mother’s serum g/dL Adult values g/dL Albumin 3.3 4.2 3.5 to 5.0 α1-Globulin 0.0 0.3 0.1 to 0.4 α2-Globulin 0.4 1.2 0.3 to 0.8 β-Globulin 0.7 1.3 0.6 to 1.1 γ-Globulin 1.0 1.3 0.5 to 1.7 Prealbumin 15 to 36 mg/dL
Distribution of the Albumin:
- Albumin makes 40% to 60% of the total proteins.
- There is a high concentration of Albumin in the plasma. Its small molecular size is found in most extravascular fluids, CSF, amniotic fluid, urine, and interstitial fluid.
- CSF protein electrophoresis show albumin around 56% to 76% of the total proteins.
- 40% of the Albumin is present in the plasma, and the other 60% is present in the extracellular space.
- Amniotic fluid contains albumin:
- Second trimester = 0.4 g/dL
- At term = 0.9 g/dL
- Around 60% of the Albumin is present in the extravascular space.
- It is highly water-soluble due to its negative charge at normal pH.
- Albumin’s half-life is 15 to 19 days. So the hepatic impairment for the synthesis of Albumin may not be detected before this period.
Synthesis of Albumin:
- A gene codes albumin on the long arm of chromosome 4.
- More than 80 genetic variants are reported.
- Albumin synthesis starts at 20 weeks of gestation and continues throughout life.
- During the first 20 weeks of fetal life, α-fetoprotein may serve as the Albumin’s osmotic equivalent.
- The liver produces 12 g of Albumin in 24 hours, representing about 25% of the total protein synthesized by the liver.
- This protein is synthesized primarily from the hepatocytes of the liver.
- It reflects the function of the liver, kidney, or malnutrition.
- The liver’s synthetic reserve is enormous, e.g., 300% or more of the normal rate in nephrotic syndrome.
- Decreased synthesis in the liver is seen in acute or chronic liver diseases, Amyloidosis, malnutrition, and malignancy.
- Dehydration leads to an increase in albumin levels (Hyperalbuminemia).
- The synthetic rate is controlled by:
- Colloid osmotic pressure.
- Protein intake.
- Decreased by the inflammatory cytokines.
- The inflammatory cytokines decrease albumin synthesis.
- Albumin Concentration in the serum at birth is 39 g/L, then it decreases to 24 g/L at nine months, again rises to 35 to 55 g/L at adult age, and after the age of 60 years is 38.3 g/L.
Albumin role as a transport protein:
- Albumin binds bilirubin, free fatty acids, calcium, and some drugs.
- Its role in transporting bilirubin, bile acids, metal ions, and drugs will be markedly affected by variation in its concentration.
- The presence of Albumin in the urine indicates kidney disease.
Mechanism of decrease in the albumin synthesis:
- The mechanism for the decrease in the serum albumin may be due to:
- Decreased synthesis may be seen in:
- Injury to the hepatocytes.
- Decreased protein intake, like malnutrition or starvation.
- If there is impaired absorption of the protein products like in sprue.
- Extensive loss of the Albumin seen in:
- In nephrotic syndrome, there is extensive loss of protein in the urine.
- There is loos of protein in the extensive burns or exfoliative dermatitis.
- In protein-losing intestinal diseases (protein-losing enteropathies).
- Shifting the protein in ascites may happen in the liver diseases like cirrhosis.
- Albumin is catabolized in various tissues.
- It is taken up by the cells as pinocytosis.
- Then, there is proteolysis from the amino acids in the cells, and these amino acids go into the body pool(recycle).
- It is susceptible to liver damage.
- Low albumin results in Edema.
- Albumin is essential for regulating water and solutes’ passage through the capillaries because the albumin molecules are large and don’t diffuse freely through the endothelium.
- Maintaining the osmotic pressure in the blood vessels is needed, without which fluids will leak out.
- One most important function is to maintain the colloid osmotic pressure of the intravascular fluid. Because of the high concentration, it is responsible for 75% to 80% of osmotic pressure. This will maintain the fluid in the tissues.
- The primary function is the maintenance of Colloidal osmotic pressure maintenance of vascular and extravascular spaces with continuous equilibrium.
- Albumin prevents edema.
- Albumin provides nutrition to the tissues and binds various molecules like salicylates, fatty acids, magnesium ions, cortisol, hormones, vitamins, and drugs.
- Albumin is a carrier protein for bilirubin, calcium, progesterone, other drugs, hormones, and enzymes.
- Drugs bound to Albumin are sulfonamide, penicillin, aspirin, and dicumarol.
- Albumin is an endogenous source of amino acids.
- Albumin binds and solubilizes nonpolar compounds such as plasma bilirubin and long-chain fatty acids.
- Albumin binds hormones like thyroxine, triiodothyronine, cortisol, and aldosterone.
- 40% of the calcium binds the Albumin.
- Some drugs like phenylbutazone, warfarin, salicylates, and clofibrate are bound tightly to Albumin.
- Low plasma albumin allows water to move out of the vascular bed and leads to edema.
- Albumin has an important role in the endogenous metabolism of calcium, fatty acids, bilirubin, drugs, and hormones.
Albumin/globulin ratio (A/G) normally found = >1.0.
- A/G ratio <1.0 is usually seen in liver diseases.
Albumin/Creatinine ratio (ACR): It evaluates patients with Diabetes Mellitus and renal function.
- Diabetic Microalbuminuria is defined when the Albumin excretion in the urine is 20 to 200 µg/min (30 to 300 mg/24 hours of the urine sample).
- These findings are found in at least 2 to 3 samples collected within six months.
- Albumin/creatinine ratio is the first lab test to detect early microalbuminuria on a random urine sample.
- It is calculated:
- Albumin in mg/creatinine in g.
- Albumin excreted in the urine is measured in µg/min (mg/24 hours), called Albumin excretion rate (AER).
- Microalbuminuria is significant when AER is 20 to 200 µg/min.
- Albumin/creatinine ratio >30 mg/g, suggests overnight excretion rate (AER) >30 µg/min.
- When 30 to 300 mg of Albumin is excreted in 24 hours of urine, the albumin/creatinine ratio is >3.4 mg/mmol.
- Creatinine in urine is measured in g.
Albumin/creatinine ratio and microalbuminuria:
|Clinical parameters||Normal values||Microalbuminuria||Clinical albuminuria|
|Albumin excretion mg/24 hours||<20 mg/day||30 to 300 mg/day||>300 mg/day|
|Albumin/creatinine ratio||<30||30 to 300||>300|
- Hyperalbuminemia is when the albumin level is higher than the normal level.
- This is seen in dehydration.
- Analbuminemia is the congenital absence of Albumin.
- These patients are usually asymptomatic or may see occasional mild edema.
- This is a rare autosomal recessive disorder.
- Serum electrophoresis shows a complete absence of the albumin band.
- Hypoalbuminemia is when the albumin level is lower than the normal, this may be due to various factors like:
- Impaired syntheses of the Albumin from the liver or decreased intake of the proteins.
- Increased catabolism due to inflammation or tissue damage.
- Due to malabsorption or malnutrition, leading to decreased absorption of the amino acids.
- There is an increased loss of Albumin in the urine in conditions like nephrotic syndrome, chronic glomerulonephritis, diabetes mellitus, and SLE.
- Protein loss in case of burn or protein-losing-enteropathy.
- In the case of ascites, where there is high pressure in the portal system, it drives the Albumin into the peritoneal cavity.
- When the albumin level is <2.0 g/L, it will lead to edema formation. This usually occurs when the albumin loss is through the urine or feces.
- Serum electrophoresis shows a low albumin spike.
Normal values of Albumin
|Type of individuals||Normal range|
|Normal range||3.4 to 5.5 g/dL (35 to 55 g/L)|
|Male||4.2 to 5.5 g/dL|
|Female||3.7 to 5.3 g/dL|
|Cerebrospinal fluid (CSF)||14 to 45 mg/dL|
|Newborn||2.8 to 4.8 g/dL|
- Another source: normal albumin values
- Recumbent adult = 3.5 to 5.0 g/dL
- Ambulatory male adult = 4.2 to 5.5 g/dL
- Ambulatory female adult = 3.7 to 5.3 g/dL
- It is lower in the last two trimesters of the pregnancy.
- The level is ∼0.3 g/dL higher in the upright position because of hemoconcentration.
- Reference ranges estimated by nephelometry:
- Newborn 2 to 4 days = 2.8 to 4.4 g/dL
- Adults = 3.4 to 5.0 g/dL
- >60 years = 3.4 to 4.8 g/dL
By serum electrophoresis, the normal values are:
|Fraction of the protein||Normal range||% of the total proteins|
|Albumin||3.5 to 5.2 g/dL||50 % to 65%|
|α1-globulin||0.1 to 0.4 g/dL||2% to 6%|
|α2-globulin||0.5 to 1.0 g/dL||6% to 13%|
|β-globulin||0.6 to 1.2 g/dL||8% to 15%|
|γ-globulin||0.6 to 1.6 g/dL||10% to 20%|
Albumin level decreases in:
- The hypoalbuminemia may take place from one of the following mechanisms:
- Impaired synthesis.
- Increased catabolism.
- Protein loss.
- Reduced absorption of the amino acids.
- Altered distribution of the albumin-like ascites.
- Severe hypoalbuminemia is due to the loss of Albumin in the urine or feces. The level is below two g/L, and edema is usually present.
- Acute and chronic inflammations:
- The cause is hemodilution, extravascular space loss, increased cell consumption, and decreased synthesis.
- Rheumatoid arthritis, granulomatous process, most bacterial infections, vasculitis, ulcerative bowel disease, and certain parasitic infestation.
- Due to decreased synthesis by the liver:
- This may be due to the increased amount of immunoglobulins and loss of Albumin into the extravascular space.
- This may also be due to decreased synthesis because of toxins or alcohol.
- The liver can compensate for Albumin synthesis, approximately 95% of liver function loss.
- In acute and chronic liver diseases, Amyloidosis, Malignancies, Congestive heart disease, and constrictive pericarditis.
- Urinary loss:
- As Albumin is relatively small and globular, a significant amount is filtered into the glomerular urine. Then the majority is reabsorbed by the proximal tubular cells.
- Normal urine contains 20 mg of Albumin per gram of creatinine.
- Excretion above this level is seen in:
- Increased glomerular filtration.
- Tubular damage.
- Or a combination of the above factors.
- Excretion above this level is seen in:
- Examples are:
- In Nephrotic syndrome.
- Thermal burns.
- Trauma and crush injuries.
- Transudation and exudation from any hollow organs.
- Increased loss via body fluids.
- Increased catabolism:
- leads to decrease albumins like fever, antimetabolites, thyrotoxicosis, and certain malignancies.
- A gastrointestinal loss:
- With the inflammatory disease of GIT.
- Chronic protein-losing enteropathy.
- Increased blood volume (hypervolemia):
- This leads to a decrease in albumins like exogenous estrogen therapy, Myeloma, and congestive heart failure.
- The serum level decreases in pregnant ladies.
- The person on a low protein diet.
- It decreases:
- After weight loss surgery.
- Whipple disease.
- Crohn’s disease.
- Analbuminemia is a rare genetic deficiency where the plasma albumin level is <0.5 g/L.
- Electrophoresis shows no albumin bands.
- Major clinical manifestations are related to abnormal lipid transport. Edema is surprisingly very mild.
- Summary of decreased Albumin:
- Hepatic diseases.
- Urinary loss.
- Gastrointestinal loss.
- Edema and ascites.
- Protein malnutrition.
Albumin level increases in:
- Naturally, there is no reason for the increase in albumin levels.
- Dehydration or any other cause leading to a decrease in the plasma volume causes an increase in the level.
- High protein diet.
- When the tourniquet is applied for a long time.
Causes of Hyperalbuminemia and Hypoalbuminemia:
|Burns||High protein diet|
|Blood loss||False value due to prolonged tourniquet|
|Decreased protein intake|