2.1: Laboratory values and biochemical correlates
- Page ID
- 37821
A comprehensive metabolic panel (CMP) is a blood test that measures a variety of compounds (such as blood glucose and electrolytes), and it can be used to determine fluid balance, kidney function, and liver function, as well as other key metabolic functions. It is often used to determine health status (or metabolic dysfunction) and gives you insight into changes in biochemical reactions. Other diagnostics such as a complete blood count (CBC) may also be used but will not be discussed here.
How to read a CMP both clinically and biochemically will help hone the skills of diagnosis and maintenance of health status in patients. Additional laboratory tests such as a lipid profile, blood lactate, or urinalysis may also be ordered to supplement information from the CMP.
Deviations in any of these values can help determine changes in substrate availability, cofactors, and vitamin or enzymatic deficiencies. It will also help you better understand how biochemical pathways can influence clinical signs and symptoms.
Comprehensive metabolic panel
A CMP is often administered as part of a routine physical exam or for monitoring of specific conditions that impact kidney and liver functions. The results include the following tests (table 2.1):
|
Analyte |
Normal range |
|---|---|
|
Chemistries |
|
|
Glucose |
70-100 mg/dl |
|
Calcium |
8.4-10.5 mg/dl |
|
Protein |
|
| Total protein | 6.1-8.0 g/dl |
| Albumin | 3.2-4.6 g/dl |
| Electrolytes | |
| Sodium | 135–144 mmol/L |
| Potassium | 3.6–5.0 mmol/L |
| Chloride | 101–111 mmol/L |
| CO2 | 21–35 mmol/L |
| Kidney test | |
| Blood urea nitrogen (BUN) | 5–20 mg/dl |
| Creatinine | 0.44–1.00 mg/dl |
| Liver tests | |
|
Alkaline phosphatase (ALP) |
38–126 IU/L |
|
Aspartate amino transferase (AST) |
14.9–39.9 IU/L |
|
Alanine amino transferase (ALT) |
11–43 IU/L |
| Bilirubin, total | 0.0–1.2 mg/dL |
| Globulin | 1.5–3.5 g/dl |
| Direct bilirubin | <0.3 mg/dl |
Glucose - This energy source for the body is maintained in a very narrow range. Metabolic pathways are in place to balance both glucose uptake and glucose output to keep this value constant. Glucose homeostasis is regulated hormonally, and deviations from normal values could suggest metabolic or hormonal deficiencies (chapter 4 and chapter 5).
Calcium - This is one of the most important minerals in the body; it is essential for the proper functioning of muscles, nerves, and cardiac tissue. It is a cofactor in processes such as blood clotting and bone formation. Other vitamins also play key roles in these pathways (vitamin K in clotting and vitamin D in bone formation), so understanding this value may give insights into other potential deficiencies.
Proteins
Albumin - Albumin is a major serum protein produced in the liver and is a nonspecific carrier of many lipid soluble vitamins and other hydrophobic compounds. It is also essential for maintaining oncotic pressure. Decreases in serum albumin may be suggestive of nutritional deficiencies or changes in plasma volume as well as poor liver function. Therefore accessibility of lipid soluble vitamins, minerals, and hormones may be diminished secondarily to a decrease in albumin.
Total protein - Like serum albumin, a measure of total serum protein is useful to evaluate malnutrition or more chronic disorders such as inflammatory bowel disease. Increased production of immunoglobulins could also be detected here and would be indicative of chronic illness.
Electrolytes
Sodium - Sodium is vital to normal body processes, including nerve and muscle function. Hyponatremia can be suggestive of illness, diarrhea, or malnutrition, while hypernatremia is most often caused by an increased loss of water (dehydration) potentially due to endocrine disorders such as Cushing syndrome or diabetes insipidus.
Potassium - Potassium is critical for cardiac function, and although hypo or hyperkalemia can be indicative of a variety of disorders, it can be a critical indicator of maintenance of diabetes. Unmanaged diabetic individuals may present with hyperkalemia, however, inappropriate insulin administration will increase potassium uptake. Therefore poor management can cause a sudden drop in potassium (hypokalemia) leading to cardiac dysfunction.
\(\ce{CO2}\) (carbon dioxide, bicarbonate) - \(\ce{CO2}\) is produced from several oxidative pathways and is removed in the form of bicarbonate or through hemoglobin transport. Elevation of \(\ce{CO2}\) could suggest a renal, respiratory, and/or metabolic concern, and additional laboratory values would need to be assessed to determine the root cause. These may include blood lactate, blood urea nitrogen (BUN), as well as arteriole blood gasses (ABG).
Chloride - Chloride is a negatively charged ion that works with other electrolytes (potassium, sodium, and bicarbonate) to help regulate both fluid and acid–base (pH) balance in the body. Chloride and electrolyte tests may help diagnose the cause of signs and symptoms such as prolonged vomiting, diarrhea, weakness, and difficulty breathing (respiratory distress).
Kidney tests
Blood urea nitrogen (BUN) - Urea is a waste product of amino acid metabolism filtered out of the blood by the kidneys. It is a primary means of nitrogen disposal, and conditions that affect the kidneys have the potential to affect the amount of urea in the blood. This value is also indicative of deficiencies in amino acid metabolism, or changes in urea cycle activity or protein catabolism (section 5.3).
Creatinine - This waste product is produced in the muscles and filtered out by the kidneys. Urinary levels of creatinine are a good indicator of how the kidneys are working.
Liver tests
Alkaline phosphatase (ALP) - ALP is an enzyme found in the liver and other tissues such as bone. Elevated levels of ALP are most commonly caused by liver disease or other pathologies that increase cell damage leading to the release of ALP in the blood. Other disorders that impact bone growth may also increase ALP.
Alanine amino transferase (ALT) - ALT is an enzyme found predominantly in the liver and kidney. It is important in movement of ammonia (through the process of transamination) in tissues, and an elevation of ALT in circulation suggests liver damage (or potentially muscle damage) (section 5.3).
Aspartate amino transferase (AST) - AST is also a transferase needed in nitrogen metabolism found especially within the heart and liver. It is also a useful test for detecting liver damage. The ratio of ALT/AST can be used to distinguish between disorders such as alcoholic versus nonalcoholic fatty liver disease (section 5.3).
Bilirubin - Bilirubin is a waste product produced by the degradation of heme. Heme degradation within the liver is a normal part of red blood cell turnover, but elevated bilirubin could also be indicative of excessive hemolysis (due to deficiencies in NAPDH or increased oxidative stress) or biliary obstructions. Bilirubin values can be reported as direct (conjugated) or indirect (unconjugated) bilirubin. As conjugation takes place in the liver, decreased conjugated bilirubin or increased unconjugated bilirubin would suggest liver dysfunction (figure 2.1).
Figure 2.1: Heme degradation.Lipid profile
A lipid profile (table 2.2) is often used to assess risk of developing cardiovascular disease (CVD) or to monitor the effectiveness of a dietary or pharmacological intervention.
| Serum measurement |
Desirable levels |
|---|---|
| Total cholesterol | <200 mg/dL |
| Low-density lipoprotein cholesterol (LDL-C) | <100 mg/dL |
| High-density lipoprotein cholesterol (HDL-C) | over 40 mg/dL for females; over 60 mg/dL for males |
| Triglycerides (TGs) | <150 mg/dL |
| TG to HDL ratio (calculated) | <5 |
Total cholesterol - This measurement takes in to account various forms of cholesterol in circulation. It is the total of high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 20 percent of the triglyceride measurement. This is key to determining your cholesterol ratio (total/HDL), which should be below 5 with an ideal ratio being 3.5.
High-density lipoprotein cholesterol (HDL-C) - HDL is predominantly involved in reverse cholesterol transport because it removes excess cholesterol from peripheral tissues and carries it to the liver for removal or use. It has several key interactions with very low-density lipid (VLDL) particles in circulation that assist in lipid metabolism.
Low-density lipoprotein cholesterol (LDL-C) - LDL is often called "bad cholesterol" because it can deposit excess cholesterol in walls of blood vessels, which can contribute to atherosclerosis.
Triglycerides - This is a measurement of circulating triacylglycerols (TAG), which are primarily transported by VLDL particles. TAG levels should be less than 150 mg/dL, and increased TAG may suggest endocrine deficiencies or metabolic defects.
Variations of normal in a lipid profile could be suggestive of heritable disorders, poor diet, or lipid uptake, decreased lipid storage, or excessive synthesis. The combination of these values will help determine what aspect of lipid metabolism is altered (chapter 6).
Lactate
Serum lactate levels may also be measured in conjunction with a complete metabolic panel. Serum lactate should be negligible under normal conditions, however, elevated lactate could be suggestive of excessive anaerobic metabolism, such as is the case in intense exercise or deficiency in oxygen transport caused by ischemic injury. This could also be caused by inappropriate diversion of substrate such as is the case in some enzymatic deficiencies (pyruvate dehydrogenase deficiency) or changes in NADH levels (figure 2.2).
Urinalysis (includes a visual, chemical, and microscopic exam)
Visual exam and the microscopic exam
Although both the visual and microscopic exam are very essential components to this analysis, these will not be focused on here. The color of urine can vary, most often shades of yellow, from very pale or colorless to very dark or amber. Red-colored urine can also occur when blood is present; yellow-brown or greenish-brown urine may be a sign of bilirubin in the urine. Urine clarity refers to how clear the urine is. This could be defined as: clear, slightly cloudy, cloudy, or turbid. "Normal" urine can be clear or cloudy.
A microscopic examination will typically be done when there are abnormal findings on the physical or chemical examination. Cells and other substances that may be seen include the following: red blood cells (RBCs), white blood cells (WBCs), epithelial cells, bacteria, yeast and parasites, trichomonas, casts, and crystals. If the crystals are from substances that are not normally in the urine, they are considered "abnormal." Abnormal crystals may indicate an abnormal metabolic process. Some of these include: calcium carbonate, cystine, tyrosine, and leucine. Urinary presence of some amino acids can be suggestive of amino acid metabolic disorders (chapter 8).
Chemical exam
Much like the CMP, the chemical analysis of a urine sample can be very indicative of biochemical derangement. A review of the following components is helpful in making a clinical diagnosis.
Specific gravity (SG) - Specific gravity is a measure of urine concentration. This test simply indicates how concentrated the urine is.
pH - Urine is typically slightly acidic, about pH 6, but can range from 4.5 to 8. The kidneys play an important role in maintaining the acid–base balance of the body. Therefore, any condition that produces acids or bases in the body, such as acidosis or alkalosis, or the ingestion of acidic or basic foods, can directly affect urine pH.
Protein - The protein test provides an estimate of the amount of albumin in the urine. Normally, there should be no protein (or a small amount of protein) in the urine. When urine protein is elevated, a person has a condition called proteinuria; this could be caused by a variety of health conditions. Healthy people can have temporary or persistent proteinuria due to stress, exercise, fever, aspirin therapy, or exposure to cold, for example.
Glucose - Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. This condition can result from either an excessively high glucose level in the blood, such as may be seen in individuals with uncontrolled diabetes. Other reducing sugars, galactose or fructose, may also be present in the urine if a metabolic deficiency occurs (section 9.1).
Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as a fasting blood glucose test are usually performed to further identify the specific cause.
Ketones - Ketones are also not normally found in the urine. They are intermediate products of fat metabolism and can be produced when an individual does not eat enough carbohydrates such as in fasting conditions or high-protein diets. When carbohydrates are not available, the body metabolizes fat to generate ATP for baseline metabolic function. Strenuous exercise, exposure to cold, frequent, prolonged vomiting, and several digestive system diseases can also increase fat metabolism, resulting in ketonuria (section 5.2).
In a person who has diabetes, ketones in urine may be an early indication of insufficient insulin. Insufficient insulin response can result in impaired glucose oxidation and consequently results in aberrant fat metabolism. Oxidation of fatty acids provides substrate for ketogenesis, which can cause ketosis and potentially progress to ketoacidosis, a form of metabolic acidosis. Excess ketones and glucose are dumped into the urine by the kidneys in an effort to flush them from the body.
Hemoglobin and myoglobin - The presence of hemoglobin in urine indicates blood in the urine (known as hematuria).
A small number of RBCs are normally present in urine, however, as these numbers elevate, this will result in a positive test result. These results are interpreted with the microscopic exam. For example, a positive test result here with no visible RBCs in the urine would suggest the presence of myoglobin only, which could be due to strenuous exercise or muscle damage.
Leukocyte esterase - Leukocyte esterase is an enzyme present in most white blood cells (WBCs). A few white blood cells are normally present in urine, however, when the number of WBCs in urine increases significantly, this screening test will become positive. When this test is positive and/or the WBC count in urine is high, it may indicate that there is inflammation in the urinary tract or kidneys.
Nitrite - Many normal bacteria can convert nitrate (normally present in urine) to nitrite (not normally present in urine). When bacteria are present in the urinary tract, they can cause a urinary tract infection, which could be diagnosed by a positive nitrite test result.
Bilirubin - Bilirubin is not present in the urine of healthy individuals (figure 2.1). The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such as jaundice develop. Only conjugated bilirubin is present in the urine.
Urobilinogen - Urobilinogen is normally present in urine in low concentrations. It is formed in the intestine from bilirubin, and a portion of it is absorbed back into the blood. Positive test results may indicate liver diseases such as viral hepatitis, cirrhosis, liver damage due to drugs or toxic substances, or conditions associated with increased RBC destruction (hemolytic anemia).
References and resources
Text
Ferrier, D. R., ed. Lippincott Illustrated Reviews: Biochemistry, 7th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2017, Chapter 27: Nutrition: Overview, Chapter 28: Micronutrients: Vitamins, Chapter 29: Micronutrients: Minerals.
Le, T., and V. Bhushan. First Aid for the USMLE Step 1, 29th ed. New York: McGraw Hill Education, 2018, 65–71.
Figures
Grey, Kindred, Figure 2.1 Heme degradation. 2021. https://archive.org/details/2.2_20210924. CC BY 4.0.
Grey, Kindred, Figure 2.2 Reaction catalyzed by lactate dehydrogenase. 2021. https://archive.org/details/2.4_20210924. CC BY 4.0.