Solving the CMP: Basic Lab Interpretation

When I wrapped up my nurse practitioner program, I remember thinking that I could have used more education around lab interpretation. Which abnormals did I need to worry about? When a lab value came back abnormal, what differential diagnoses could be causing the abnormality? I tell participants in MidlevelU's programs that one could get a PhD in lab interpretation - there can be a high degree of complexity in understanding how some of the physiologic systems involved work. So, we master the basics to start, then build on interpretation ability throughout our careers. 

If you feel that your lab interpretation skills could use a brush-up, here's a quick guide to the complete metabolic panel (CMP). 

Why order a CMP?

Essentially, the complete metabolic panel looks at glucose, kidney function, electrolytes, acid/base balance, proteins and liver function. So, if you're interested in the function of any of these body systems, a CMP is in order. The image below shows what lab values coordinate with which organ function. 

What's the difference between a BMP and a CMP?

The complete metabolic panel (CMP) gives more information than the basic metabolic panel (BMP)...obviously! What additional information does it give? The CMP includes the same labs as the BMP plus liver function (AST, ALT), proteins (albumin, total protein), bilirubin and alkaline phosphatase. 

If the CMP gives more information, why not order it over the BMP every time?

I get it. I'm a more-is-better kind of person, too. The temptation is to order a CMP whenever you need to check out any kind of chemistries. But, there are two reasons more information is not always better:

1. Cost - Ordering more tests costs your patient more money. In the case of the BMP vs. CMP questions, this might only mean a few bucks, but that is a meaningful amount to some patients. 

2. Testing Ramifications - If a lab comes back abnormal, you'll need to do something about it. It's always best to hone your testing in on what you truly think needs to be evaluated. Otherwise, you might end up spending time and resources chasing down irrelevant abnormal results. 

Alright, now that we've had an overview, what does each of the lab values in a CMP mean? How should they be interpreted and when is an abnormal deemed dangerous?

Let's take each lab value contained within the CMP one-at-a-time...

Glucose

Reference Range: 70-99mg/dL (fasting) 

You're all probably pretty familiar with glucose. The lab measures the amount of circulating glucose in the blood. We order this test to screen for hyper and hypoglycemia and especially as part of monitoring diabetic patients. 

A few glucose quick facts that might come in handy: 

  • A slight increase is normal with aging.
  • Increased levels may be a sign of diabetes, Cushing's syndrome, pancreatitis, thiazide diuretics, infection or steroid use.
  • Decreased levels may signal liver disease, malnutrition, sepsis or an endocrine tumor.

Sodium 

Reference Range: 135-145 mmol/L

Sodium is an electrolyte present in all bodily fluids. It helps regulate the amount of fluid that is excreted or retained and also plays a role in nerve and muscle function. Sodium levels are usually inversely related to the amount of fluid in the body (i.e. low sodium = too much fluid; high sodium = too little fluid). So, when you see sodium levels that fall outside of normal range you should think "uh oh, we've got a fluid problem here". Your initial differentials will be based on diagnoses that cause fluid retention (ex. CHF) or excretion (ex. diabetes insipidus)/ lack of fluid intake (ex. in elderly or immobilized patients). 

Small deviations from the reference range are okay - mild hyponatremia is defined as a sodium of 130-134 mmol/L. Large deviations from normal can be a serious problem. Patients who are symptomatic, or with severe hypo/hypernatremia may require hospitalization. 

Potassium 

Reference Range: 3.5 -5.1 mEq/L

Potassium is vital to cell metabolism. It helps transport nutrients into and out of cells and also helps transmit impulses from nerve to muscle cells. Potassium levels may be decreased with diuretic use, vomiting, diarrhea and/or with deficient intake. Potassium levels may be increased in kidney failure (causes decreased excretion in the urine), in dehydration, with ACE inhibitor or Spironolactone use, or related to excessive potassium intake. 

Because potassium is essential for transmission of impulses from nerve to muscle cells and the heart is a muscle, significant variations in potassium can be fatal. Hyperkalemia (elevated potassium levels) can cause cardiac arrhythmias. Deviations from normal, other than those that are quite small, are therefore not acceptable and mandate further workup and/or treatment. 

A quick tip for potassium. Potassium values are sensitive to collection and processing errors. Actions like aggressive fist-pumping before a lab draw or shaking lab vials can result in falsely elevated levels. So, you may want to recheck levels for accuracy if you get a potassium result back that doesn't make sense. 

Chloride

Reference Range: 98-106 mEq/L

Chloride helps regulate acid/base balance and fluid levels in the body. Typically, levels of chloride correlate with sodium so you'll notice that if a patient's chloride levels are off, their sodium is respectively high or low as well. Since chloride is involved in regulation of pH, you'll see abnormal levels in alkalotic or acidotic states. Kidney disease and dehydration can also affect chloride values. 

A few chloride interpretation quick tips: 

  • This lab value is almost never ordered or evaluated alone, rather compare with sodium and other CMP values for a more complete clinical picture. 
  • Critical values for chloride are <70 or >120 mmol/L. So, small deviations from the normal range are okay. 

Carbon Dioxide

Reference Range: 23-29 mEq/L

Carbon dioxide is critical for regulating acid/base balance in the body. Most carbon dioxide is in the form of bicarbonate. In clinical practice, bicarbonate level in conjunction with the electrolyte panel gives us a good picture of the patient's acid/base balance status. Small deviations from normal are okay, but with any moderate elevation or decrease, your next step should order blood gasses to evaluate the severity of the imbalance. 

Calcium 

Reference Range: 8.9-10.1 mg/dL

When it comes to the CMP, the value we're looking at here is the amount of calcium circulating in the bloodstream. About 99% of the body's calcium is in the bones. The 1% that circulates in the bloodstream helps with cell function including muscle contractility an nerve function. Abnormal levels can indicate a parathyroid disorder, absorption problem, vitamin D excess/deficiency and kidney disease.

Calcium levels can also be tired to albumin levels. Albumin, a protein, is responsible for calcium transportation. When we lack albumin, we cannot transport calcium effectively and may see decreased blood levels.  

When calcium is out of whack, check the following corresponding values to help get to the root of the problem: 

  • Phosphorous
  • Magnesium
  • Vitamin D 
  • Parathyroid Hormone
  • Urine Calcium 

Small deviations from normal are okay when it comes to calcium. Look for an underlying cause, repeat labs and look for trends. 

Total Protein 

Reference Range: 6.3-7.9 g/dL

Proteins are essential building blocks of tissues required for growth development and essential physiologic functions. In the CMP, we measure albumin and globulin, which together make up the total protein value. 60% of protein in circulation is albumin and 40% is globulin. 

Variations in the total protein value (or concentration) result from one of two things - a change in plasma volume or a change in one or more of the specific proteins in the plasma. Total protein may be increase in conditions with high protein production like multiple myeloma, or in states of decreased plasma volume like dehydration or inflammation/infection. Total protein may be decreased when production of albumin or globulin is impaired such as in severe liver disease, in conditions that accelerate loss of protein like kidney disease, in conditions that increase plasma volume such as CHF, and in malnutrition or malabsorptive states. 

Overall, some deviation from the reference range is okay. Monitor carefully and consider the total protein value in conjunction with results of albumin and globulin specifically. 

Albumin 

Reference Range: 3.5-5 g/dL

Albumin is a protein synthesized by the liver. It is the most abundant protein in the body and is required for tissue growth and repair. It is also responsible for transportation of hormones, vitamins, drugs and other substances throughout the body. Overall, albumin serves as an indicator of kidney function, liver function and how well the diet provides protein (although prealbumin is the gold standard for predicting nutritional state). 

Decreased albumin is most likely caused by kidney disease. To a lesser extent, it may also be caused by liver disease as this is where albumin production occurs. Increased values may be caused by dehydration. Check kidney and liver function in relation with albumin These values are likely to help you determine the cause of an abnormal value. 

Globulin

Reference Range: 2.5-3.5 g/dL

Globulin makes up the remaining 40% of protein in the plasma. It includes enzymes, antibodies, hormones, carrier proteins, and other various proteins. This family of proteins is produced by the liver or immune system. Decreased values signal malnutrition, liver disease or kidney disease. Increased values suggest autoimmune disease or inflammatory conditions like multiple myeloma, leukemia, rheumatoid arthritis and lupus. 

Albumin/Globulin Ratio

Reference Range: Slightly greater than 1.0 

Since 60% of circulating protein is albumin and 40% is globulin, the Albumin:Globulin ratio should be slightly greater than 1.0. If the ratio is off, you likely have over or under production of one of the protein families. Look at the specific protein values to determine the underlying cause of the shift in the A/G ratio.

BUN (Blood Urea Nitrogen) 

Reference Range: 3-20 mg/dL

Urea is a waste product formed in the liver during protein metabolism. This byproduct is then released by the liver, filtered by the kidneys and excreted in urine. So, we can use urea levels as a measure of kidney (and to a lesser degree liver) function. 

A few clinical tips as it relates to BUN: 

  • BUN increases slightly with normal aging and is also slightly higher in males than in females (related to larger muscle mass). 
  • Small deviations from the reference range are okay. Compare present values to prior labs to evaluate for a trend of decreased kidney function. 

BUN can be increased in impaired kidney function, with decreased blood flow to the kidneys (think CHF, dehydration) and with high protein diets. BUN may be decreased in starvation states, liver failure and with low protein intake. 

Creatinine

Reference Range: Male 0.5-1.2 mg/dL; Female 0.4-1.1 mg/dL

Creatinine is a waste product formed by the muscles during the process of energy production. The amount of creatinine an individual forms on a daily basis is related to muscle mass and therefore varies based on ethnicity, age and gender. Creatinine is then filtered and secreted by the kidneys and released in the urine. As a diagnostic tool, creatinine measures kidney function. 

Creatinine values may be increased in kidney disease and decreased in liver disease or in states of muscle wasting. A few helpful hints as you evaluate creatinine levels: 

  • Compare current values to previous lab results and look at individual trends. Because creatinine is dependent on muscle mass, a single value can be misleading. 
  • A normal serum creatinine may not be normal. Because the value is dependent on individual body habitus, even a value that falls within the normal reference range may indicate decreasing kidney function for a specific patient. Compare to prior lab results. 

BUN/Creatinine Ratio 

Reference Range: Between 10:1 and 20:1

Looking at the BUN/creatinine ratio can further aid in distinguishing which disease state may be causing abnormal lab values. The BUN:creatinine ratio usually remains normal in chronic kidney disease. A BUN:creatinine ratio that is >20 suggests dehydration or another state that causes decreases renal perfusion. A BUN:creatinine ratio >30 can suggest a GI bleed.

GFR (Glomerular Filtration Rate) 

Reference Range: >90 ml/min

GFR is the optimal measure of kidney function and helps detect early kidney damage (as opposed to creatinine whose levels increase only after significant loss of kidney function). Glomerular filtration rate takes into account serum creatinine levels along with variables like gender, age, weight and race. Some clinical pearls to keep in mind: 

  • The GFR calculation may not be valid in some patients such as those who are very elderly, pediatric patients, pregnant individuals, patients with extremes of body habitus, malnutrition, paraplegia, skeletal muscle disease and those with rapidly changing kidney function.
  • If GFR is abnormal for the first time (and isn't too low), repeat the lab in 1-3 months. If GFR remains abnormal, check a urine microalbumin. Proteinuria might signal kidney disease and should be followed up accordingly. As always, whenever you look at GFR, take the entire lab picture into account in making your clinical decisions. 

Bilirubin

Reference Range: 0.2-1.2 mg/dL (total) 

Bilirubin is a waste product of the normal breakdown of heme, a component of hemoglobin. It is processed by the liver then eliminated from the body. So, serum bilirubin levels are an indicator of liver function and to a lesser extent hematologic disorders. Elevated bilirubin levels can be classified into 3 possible causes:

  1.  Prehepatic (increased bilirubin production) - common in hematologic disorders like thalassemia, mesoblastic anemia, porphyria
  2. Hepatic (liver dysfunction) - common in cirrhosis, CHF and with certain drugs
  3. Posthepatic (duct obstruction) - common in malignancies, pancreatitis, cholecystitis

Be aware of Gilbert Syndrome. This is an interesting clinical finding in which an otherwise healthy individual has elevated bilirubin with normal liver function, a normal CBC, and an absence of other disease processes. 

Alkaline Phosphatase

Reference Range: 44-147 IU/L

Alkaline phosphatase (ALP) is an enzyme found in numerous body tissues but primarily in the liver and bone. In the liver, ALP is present externally on the cells that form the bile ducts. When these cells become blocked or inflamed, such as in cholecystitis, liver cancer or liver disease, you will notice increased ALP levels. Alkaline phosphatase may also be elevated in conditions that cause excessive bone growth like Paget's disease.

Here are a few interpretation pearls related to alkaline phosphatase:

  • Specimen handling can affect levels so small deviations from normal are OK; clinically significant elevation of ALP is usually about three times normal
  • In hepatitis and with heavy alcohol consumption, ALP is usually about two times normal range
  • ALP is expected to be high in children related to rapid bone growth

If alkaline phosphatase is elevated in the absence of other abnormalities (lab, exam, whole clinical picture), repeat the test in 6 to 12 months. 

AST

Reference Range: Males 6-34 IU/L Females 8-40 IU/L

Aspartate aminotransferase (AST) is an enzyme that plays a role in energy production found primarily in the liver and heart and in smaller amounts in the muscles, brain, pancreas and kidneys. When these organs are damaged, AST is released into the bloodstream with serum levels paralleling the extent of damage. While AST is typically thought of as a liver enzyme, remember that the enzyme can reflect abnormalities in other organs.. For example, muscle damage or even strenuous exercise can cause elevated AST. 

Conditions most likely to cause increased AST include hepatitis, toxins/drugs, chronic liver disease, alcohol abuse, heart or kidney damage, muscle injury and cirrhosis. Typically, you can have a low level of concern until AST levels are over 100. Acute or viral hepatitis, for example, result in AST levels about 10 times normal ranges, and even 100 times normal in liver toxicity. Following an acute attack, it can take these levels about 2-4 months to return to normal. 

ALT

Reference Range: 20-60 IU/L 

Alanine aminotransferase (AST) is an enzyme located primarily in the liver and kidney and most commonly associated with liver function. It is more specific to liver function than AST. Elevated AST can signal acute hepatitis, toxins/drugs, chronic liver disease, alcohol abuse, kidney damage, muscle injury and cirrhosis. Clinical takeaways are similar to those of AST. 

AST/ALT Ratio

Looking at the AST/ALT ratio can be helpful in determining the cause of elevated enzymes. The so called "De Ritis Ratio" indicates the pathology behind elevated AST to ALT values. For example, an AST/ALT ratio of 2:1 or greater can be suggestive of alcoholic liver disease.

 

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