What Alkaline Phosphatase, Globulin, and Total Protein Measure on a CMP
Alkaline Phosphatase (ALP)
Alkaline phosphatase is a membrane-bound enzyme produced primarily in the liver and bone, with additional sources including intestines, kidneys, and placenta during pregnancy. 1
Tissue Sources and Clinical Significance
- ALP is produced in multiple tissues including liver, bone, intestines, kidneys, and placenta, with liver and bone being the predominant sources in non-pregnant adults 1
- The enzyme is often associated with cell membranes, though its exact physiologic function remains unknown 2
- In liver disease, particularly cholestatic conditions (bile duct obstruction or dysfunction), ALP elevation reflects impaired bile flow and hepatobiliary pathology 3
- In bone disorders, ALP elevation indicates increased osteoblastic activity seen in conditions like Paget's disease, osteoporosis, bone metastases, fracture healing, and normal bone growth in children 1, 2
Interpreting ALP Elevation
- When ALP is elevated with normal gamma-glutamyl transferase (GGT), this strongly suggests a non-hepatic source, most commonly bone, because GGT is found in liver but not in bone 1
- ALP isoenzyme fractionation can determine the percentage derived from liver versus bone or other tissues when the source is unclear 1
- In pregnancy, ALP physiologically increases beginning in the second trimester due to placental production, reaching up to twice the upper limit of normal—this is expected and does not indicate pathology 4
- Avoid unnecessary hepatic imaging when GGT is normal with elevated ALP, as this strongly indicates a non-hepatic source 1
Age and Physiologic Variations
- ALP increases by 20% between the 3rd and 8th decade of life 3
- Children have physiologically higher ALP levels due to bone growth 4
- Pregnant women have elevated ALP from placental production starting in the second trimester 4
Globulin
Globulin represents a heterogeneous group of serum proteins including immunoglobulins (antibodies), transport proteins, and acute phase reactants—elevated levels suggest immune activation, chronic inflammation, or liver disease.
What Globulin Measures
- Globulin is calculated by subtracting albumin from total protein (Globulin = Total Protein - Albumin) 3
- The globulin fraction includes gamma globulins (immunoglobulins IgG, IgA, IgM), alpha and beta globulins (transport proteins, complement, acute phase reactants) 3
- In autoimmune hepatitis, total serum globulin or gamma-globulin or IgG concentrations greater than 1.5 times the upper normal limit support the diagnosis 3
Clinical Significance of Elevated Globulin
- Elevated globulin indicates increased immunoglobulin production from chronic infection, autoimmune disease, or chronic liver disease 3
- In liver disease, particularly cirrhosis and autoimmune hepatitis, polyclonal hypergammaglobulinemia occurs due to impaired hepatic clearance of antigens and immune dysregulation 3
- Monoclonal elevations suggest plasma cell disorders like multiple myeloma or monoclonal gammopathy of undetermined significance 3
Population Variations
- Black participants have significantly higher normal ranges in globulin compared to White participants 3
- These racial differences in laboratory reference ranges should be considered when interpreting results to avoid misclassification 3
Total Protein
Total protein measures the combined concentration of albumin and globulin in serum, reflecting hepatic synthetic function, nutritional status, and immune system activity.
Components and Measurement
- Total protein consists of albumin (approximately 60%) and globulin (approximately 40%) 3
- The liver synthesizes most serum proteins including albumin and many globulins 3
- Total protein assessment includes albumin measurement, with globulin calculated by subtraction 3
Clinical Significance
- Low total protein suggests decreased hepatic synthesis (chronic liver disease, malnutrition), protein loss (nephrotic syndrome, protein-losing enteropathy), or hemodilution 3
- High total protein typically reflects elevated globulin from immune activation, dehydration, or monoclonal gammopathy 3
- In liver disease assessment, total protein is evaluated alongside albumin, bilirubin, and coagulation studies to assess hepatic synthetic function 3
Physiologic Variations
- Total protein shows significant differences between males and females 3
- Black participants have significantly higher normal ranges in total protein compared to White participants 3
- During pregnancy, total body protein actually increases by approximately 925 grams despite lower serum concentrations due to hemodilution 4
Monitoring Context
- Total protein is routinely monitored in comprehensive metabolic panels for patients on parenteral antimicrobial therapy, those with liver disease, and cancer patients undergoing treatment 3
- In tyrosinemia type I, the CMP (which includes total protein) is part of routine clinical monitoring to assess liver function and disease progression 3