A/G Ratio - Kresser Institute Membership Site

Marker Name: A/G Ratio

REFERENCE RANGES FOR A/G RATIO:

Laboratory reference range: 1.1–2.5

Functional reference range: 1.5–2.0

DESCRIPTION:

Blood contains two major classes of circulating proteins: albumin and globulins.¹ The mathematical ratio of albumin to globulin in the serum is the A/G ratio.² Under normal conditions, 60 percent of plasma protein in a given sample is albumin, while the remaining 40 percent is globulins.³ Plasma globulins and albumin are synthesized by the liver, while immunoglobulins are synthesized by cells of the immune system.⁴

Albumin performs several functions in the intravascular space. It provides osmotic pressure, which helps retain water in the vasculature. It also acts as a carrier protein for a number of substances including calcium, unconjugated bilirubin, thyroid hormones, and a multitude of pharmaceutical drugs.^4,5 Globulins are a heterogeneous assortment of circulating proteins that includes enzymes, proteins of the complement system, clotting factors, and immunoglobulins.^1,3,6 Immunoglobulins make up a substantial fraction of the total globulin content in blood.^1,6 As such, albumin and immunoglobulin levels drive much of the A/G ratio.

Levels of albumin and globulin are regulated in separate ways. Albumin is synthesized at a constant rate by the liver and has a long half-life compared to other proteins, especially in tissues.⁷ Immunoglobulin levels in blood are constant in the absence of an active immune response. This immune response can be a reaction to an acute infection or chronic autoimmune inflammation. Immunoglobulin levels can also be elevated from a neoplastic conversion of immune cells (e.g., plasma cells in multiple myeloma).⁸

The A/G ratio is a calculation based on a directly measured level, albumin, and a calculated level, globulin. Total protein is the combined quantity of albumin and globulins in serum, but it is not measured as the sum of two measured substances. Instead, total protein is the quantity of all molecules in a serum sample that contain peptide bonds. In other words, total protein and albumin are directly measured in a standard liver panel and globulins are not.³ Globulin levels are calculated by subtracting the albumin level from the total protein level. The albumin level divided by the calculated globulin level provides the A/G ratio.²

An elevated A/G ratio could theoretically signify abnormally high levels of albumin or abnormally low levels of globulins. In practice, however, an elevated A/G ratio virtually always signifies a deficiency in one or more types of globulins.³ With the exception of extremely rare clinical situations (e.g., hepatocellular carcinoma that increases albumin biosynthesis), albumin production by the liver is either normal or inappropriately low.^3,9 Albumin levels can increase during periods of dehydration and relative hemoconcentration; however, globulin levels will also increase in periods of decreased intravascular water. Therefore, the ratio of albumin to globulin would remain unchanged. Most often, a high A/G ratio reflects underproduction of immunoglobulins.^10,11

An abnormally low A/G ratio indicates either albumin deficiency or globulin excess in serum. Albumin levels may be abnormally low because of lack of production by the liver (e.g., cirrhosis) or from protein wasting (e.g., nephrotic syndrome).⁴ Importantly, hypoalbuminemia due to renal protein loss must be greater than globulin loss to appreciably lower the A/G ratio. Globulin levels may increase in serum from inflammation or infection, or the increase could reflect hematologic cancer, such as Waldenstrom macroglobulinemia.⁴

A standard liver panel includes total protein, albumin, alanine aminotransferase (ALT), acetate aminotransferase (AST), alkaline phosphatase, and bilirubin.¹² The report may also provide a calculated A/G ratio.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^10,11

Immunoglobulin deficiency (e.g., agammaglobulinemia, chronic lymphocytic leukemia)

Low in:⁴

Albumin deficiency
- Liver cirrhosis
- Nephrotic syndrome
- Analbuminemia
Globulin excess
- Acute infection/inflammation
- Chronic inflammatory disease (e.g., tuberculosis, syphilis)
- Hematological neoplasm
  - Multiple myeloma
  - Monoclonal gammopathy of undetermined significance
  - Lymphoma
  - Leukemia
  - Macroglobulinemia (e.g., Waldenstrom macroglobulinemia)

FUNCTIONAL RANGE INDICATIONS:

High in:

Same as conventional indications

Low in:

Same as conventional indications

References: