Albumin (Serum Albumin)

What sample is needed for serum Albumin?

1. It is done on the patient’s serum.
2. How to get good serum?
   1. Take 3 to 5 ml of blood in a 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.
3. A random sample can be taken.
4. You can use a freshly prepared serum or store it at 4 °C, which may keep it stable for more than 72 hours.

What are the precautions for Albumin?

1. A fasting sample is preferred.
2. Specimens with lipemia or hemolysis should be avoided.
3. Avoid prolonged tourniquet. This may increase Albumin and proteins.
4. Take into account physical exercise and fever where there is increased filtration.
5. Blood samples after the I/V therapy may give low value.
6. The drugs that increase the level are anabolic steroids, androgens, corticosteroids, insulin, progesterone, and growth hormone.
7. The drugs that can decrease the level are estrogens, hepatotoxic drugs, and oral contraceptives.

What are the indications for serum albumin?

1. This test is advised for:
   1. In liver diseases as a part of a liver panel test.
   2. Kidney diseases and nephrotic syndrome patients.
   3. In patients with a severe burn.
   4. As a part of other tests.
   5. In a patient suspected of malnutrition.
   6. In patients where there is a loss from the intestine.
   7. Patients with cancers, particularly lymphoma and multiple myeloma.
   8. Albumin is estimated in the third trimester of pregnancy, which may decrease the total protein level.

How will you discuss the pathophysiology of Albumin?

1. This is the most abundant protein in the blood.
   1. Albumin is the most abundant protein in the plasma, constituting 2/3 of total proteins. It is present in around 40% of the plasma and 60% of the extracellular space.
2. Plasma proteins are separated into three major groups:
   1. Fibrinogen (4%).
   2. Globulins (38%).
   3. Albumin (58%).
   4. Total serum proteins are a combination of prealbumin, Albumin, and globulins.

What is the Albumin structure?

1. Albumin is a globular protein with a molecular mass of 66.3 kD.
2. Albumin consists of one polypeptide chain of 585 amino acids and contains 17 disulfide bonds.
3. Albumin is an anion at pH 7.4 with >200 negative charges per molecule.
4. It has no carbohydrate side chains but is highly soluble in water due to its high net negative charge at physiologic pH.
   1. Albumin can not be stored in the parenchymal cells because of a lack of side Carbohydrate chains.
5. It accounts for approximately half of the plasma proteins.
6. This is the major protein component of most extravascular body fluids like CSF, urine, amniotic fluid, and interstitial fluid.

How would you discuss the serum electrophoresis?

• The most common method to separate the proteins is electrophoresis. There are five bands named:
  1. Albumin.
     1. It is roughly 60% of the total serum proteins and will migrate farthest toward the anode.
  2. α1- fraction.
  3. α2- fraction.
  4. β- fraction.
  5. γ- fraction.

What are the proteins in the blood, cord blood,  and serum?

What is the distribution of the Albumin in the body?

1. Albumin makes 40% to 60% of the total proteins.
2. There is a high concentration of Albumin in the plasma.
3. Its small molecular size is found in most extravascular fluids, CSF, amniotic fluid, urine, and interstitial fluid.
4. CSF protein electrophoresis shows albumin around 56% to 76% of the total proteins.
5. 40% of the Albumin is present in the plasma, and the other 60% is in the extracellular space.
6. Amniotic fluid contains albumin:
   1. Second trimester = 0.4 g/dL
   2. At term = 0.9 g/dL
7. Around 60% of the Albumin is present in the extravascular space.
8. It is highly water-soluble due to its negative charge at normal pH.
9. Albumin’s half-life is 15 to 19 days.
10. So, hepatic impairment during the albumin synthesis may not have been detected before this period.

How is the synthesis of Albumin?

1. A gene codes albumin on the long arm of chromosome 4.
2. More than 80 genetic variants are reported.

3. Albumin synthesis starts at 20 weeks of gestation and continues throughout life.
   1. During the first 20 weeks of fetal life, α-fetoprotein may serve as the Albumin’s osmotic equivalent.
   2. The liver produces 12 g of Albumin in 24 hours, representing about 25% of the total protein synthesized by the liver.
4. This protein is synthesized primarily from the hepatocytes of the liver.
5. It reflects the function of the liver, kidney, or malnutrition.
6. The liver’s synthetic reserve is enormous, e.g., 300% or more of the normal rate in nephrotic syndrome.
7. Decreased synthesis in the liver is seen in acute or chronic liver diseases, Amyloidosis, malnutrition, and malignancy.
8. Dehydration leads to an increase in albumin levels (Hyperalbuminemia).

How the synthetic rate is controlled?

1. Colloid osmotic pressure.
2. Protein intake.
3. Decreased by the inflammatory cytokines.
4. The inflammatory cytokines decrease albumin synthesis.
5. Albumin Concentration in the Serum:
   1. At birth, it 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 60 years, it is 38.3 g/L.

What is the role of Albumin as a transport protein?

1. Albumin binds bilirubin, free fatty acids, calcium, and some drugs.
   1. Variations in its concentration will markedly affect its role in transporting bilirubin, bile acids, metal ions, and drugs.

2. The presence of Albumin in the urine indicates kidney disease.

What is the mechanism of decrease in the albumin synthesis?

1. The mechanism for the decrease in serum albumin may be due to decreased synthesis due to:
   1. Injury to the hepatocytes.
   2. Decreased protein intake, like malnutrition or starvation.
   3. If there is impaired absorption of the protein products, such as in sprue,
2. Extensive loss of the Albumin seen in:
   1. In nephrotic syndrome, there is extensive loss of protein in the urine.
   2. There is a loss of protein in extensive burns or exfoliative dermatitis.
   3. In protein-losing intestinal diseases (protein-losing enteropathies).
3. Shifting the protein in ascites may happen in the liver diseases like cirrhosis.

How will you discuss the Albumin catabolism?

1. Albumin is catabolized in various tissues.
2. It is taken up by the cells as pinocytosis.
3. Then, there is proteolysis from the amino acids in the cells, which (amino acids) go into the body pool (recycle).

What are the Albumin functions?

1. It is susceptible to liver damage.
2. Low albumin results in Edema.
3. 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.
4. Maintaining the osmotic pressure in the blood vessels is needed, without which fluids will leak out.
   1. One of the most important functions is maintaining the colloid osmotic pressure of the intravascular fluid.
   2. Because of its high concentration, it is responsible for 75% to 80% of osmotic pressure, which maintains the fluid in the tissues.
   3. The primary function is maintaining colloidal osmotic pressure in vascular and extravascular spaces with continuous equilibrium.
5. Albumin prevents edema.
6. Albumin provides nutrition to the tissues and binds various molecules, such as salicylates, fatty acids, magnesium ions, cortisol, hormones, vitamins, and drugs.
7. Albumin is a carrier protein for bilirubin, calcium, progesterone,  other drugs, hormones, and enzymes.
   1. Drugs bound to Albumin are sulfonamide, penicillin, aspirin, and dicumarol.
8. Albumin is an endogenous source of amino acids.
9. Albumin binds and solubilizes nonpolar compounds such as plasma bilirubin and long-chain fatty acids.
10. Albumin binds hormones like thyroxine, triiodothyronine, cortisol, and aldosterone.
11. 40% of the calcium binds the Albumin.
12. Some drugs like phenylbutazone, warfarin, salicylates, and clofibrate are bound tightly to Albumin.
13. Low plasma albumin allows water to move out of the vascular bed, leading to edema.
14. Albumin is important in the endogenous metabolism of calcium, fatty acids, bilirubin, drugs, and hormones.

What is the albumin/globulin ratio (A/G)?

1. It is normally found = >1.0.
2. A/G ratio <1.0 is usually seen in liver diseases.

What is the Albumin/Creatinine ratio (ACR)?

• It evaluates patients with Diabetes Mellitus and renal function.

How will you differentiate the Albumin/creatinine ratio and microalbuminuria?

How will you discuss the Diabetic Microalbuminuria?

1. It 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).
2. These findings are found in at least 2 to 3 samples collected within six months.
   1. The albumin/creatinine ratio is the first lab test to detect early microalbuminuria on a random urine sample.
3. It is calculated as:
   1. Albumin in mg/creatinine in g.
4. Albumin excreted in the urine is measured in µg/min (mg/24 hours), and this is called the Albumin excretion rate (AER).
   1. Microalbuminuria is significant when AER is 20 to 200 µg/min.
   2. An albumin/creatinine ratio >30 mg/g suggests an overnight excretion rate (AER) >30 µg/min.
      1. When 30 to 300 mg of Albumin is excreted in 24 hours of urine, the albumin/creatinine ratio is >3.4 mg/mmol.
5. Creatinine in urine is measured in g.

What are the causes of Hyperalbuminemia?

1. It is when the albumin level is higher than the normal level.
   1. This is seen in dehydration.

What are the causes of Analbuminemia?

1. It is the congenital absence of Albumin.
2. These patients are usually asymptomatic or may see occasional mild edema.
3. This is a rare autosomal recessive disorder.
4. Serum electrophoresis shows a complete absence of the albumin band.

What are the causes of Hypoalbuminemia?

1. It is when the albumin level is lower than normal; this may be due to various factors like:
   1. Impaired syntheses of the Albumin from the liver or decreased intake of the proteins.
   2. Increased catabolism due to inflammation or tissue damage.
   3. Malabsorption or malnutrition leads to decreased absorption of amino acids.
   4. There is an increased loss of Albumin in the urine in conditions like nephrotic syndrome, chronic glomerulonephritis, diabetes mellitus, and SLE.
   5. Protein loss in case of burn or protein-losing-enteropathy.
   6. In the case of ascites, where there is high pressure in the portal system, the Albumin is driven into the peritoneal cavity.
   7. 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.
   8. Serum electrophoresis shows a low albumin spike.

What are the normal values of Albumin?

• 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

What are the proteins by serum electrophoresis?

What are the causes of decreased Albumin levels?

1. Hypoalbuminemia may take place from one of the following mechanisms:
   1. Impaired synthesis.
   2. Increased catabolism.
   3. Protein loss.
   4. Reduced absorption of the amino acids.
   5. Altered distribution of the albumin-like ascites.
      1. 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.
2. Acute and chronic inflammations:
   1. The causes are hemodilution, extravascular space loss, increased cell consumption, and decreased synthesis.
   2. Rheumatoid arthritis, granulomatous process, most bacterial infections, vasculitis, ulcerative bowel disease, and certain parasitic infestation.
3. Due to decreased synthesis by the liver:
   1. This may be due to the increased amount of immunoglobulins and loss of Albumin into the extravascular space.
   2. This may also be due to decreased synthesis because of toxins or alcohol.
   3. The liver can compensate for Albumin synthesis, which causes approximately 95% of liver function loss.
      1. In acute and chronic liver diseases, Amyloidosis, Malignancies, Congestive heart disease, and constrictive pericarditis.
4. Urinary loss:
   1. As Albumin is relatively small and globular, a significant amount is filtered into the glomerular urine.
   2. The majority is then reabsorbed by the proximal tubular cells.
   3. Normal urine contains 20 mg of Albumin per gram of creatinine.
   4. Excretion above this level is seen in the following:
      1. Increased glomerular filtration.
      2. Tubular damage.
      3. Hematuria.
      4. Or a combination of the above factors.
   5. Examples are:
      1. In  Nephrotic syndrome.
      2. Thermal burns.
      3. Trauma and crush injuries.
      4. Transudation and exudation from any hollow organs.
      5. Increased loss via body fluids.

4. Due to Increased catabolism:
   1. This leads to decreased albumin-like fever, antimetabolites, thyrotoxicosis, and certain malignancies.
5. Due to gastrointestinal loss:
   1. With the inflammatory disease of GIT.
   2. Chronic protein-losing enteropathy.
6. Due to Increased blood volume (hypervolemia):
   1. This leads to decreased albumin-like exogenous estrogen therapy, Myeloma, and congestive heart failure.
   2. The serum level decreases in pregnant ladies.
   3. The person is on a low-protein diet.
7. Albumin is decreased in the following:
   1. After weight loss surgery.
   2. Whipple disease.
   3. Sprue.
   4. Crohn’s disease.
8. Analbuminemia is a rare genetic deficiency where the plasma albumin level is <0.5 g/L.
   1. Electrophoresis shows no albumin bands.
   2. Major clinical manifestations are related to abnormal lipid transport. Edema is surprisingly very mild.
9. How will you summarize decreased Albumin?
   1. Inflammations.
   2. Hepatic diseases.
   3. Urinary loss.
   4. Gastrointestinal loss.
   5. Edema and ascites.
   6. Protein malnutrition.

 What are the causes of increased Albumin levels?

1. Naturally, there is no reason for the increase in albumin levels.
2. Dehydration or any other cause leading to a decrease in the plasma volume causes an increase in the level.
3. High protein diet.
4. When the tourniquet is applied for a long time.

What are the causes of  Hyperalbuminemia and Hypoalbuminemia?