Laboratory Tests – 2

Last posting we discussed the CBC and ESR. Today we’ll delve into the Comprehensive Metabolic Panel (CMP). Our goal is not to go through a textbook differential diagnosis of all lab abnormalities, but mainly to highlight significant curiosities to take into consideration when initially interpreting results.

In terms of textbooks, it’s all in cyberspace now. I rely mainly on UpToDate®, which is expensive but worth the price. is also good; since I never remember my free log-in nor password, I simply Google “hypercalcemia emedicine”. I’m sure you all have your own favorites as well.

So now we’ll begin our peek at the CMP with, randomly,…


Potassium — Anyone who’s ever taken call has surely been awakened for an elevated potassium incompatible with life, due to in vitro hemolysis, although lab technicians should be able to see and report this after centrifuging. The occurrence of both very high potassium and very low glucose (like <40) in an asymptomatic person clinches the conclusion.

Of course, bona fide in vivo hemolysis can cause clinically-important hyperkalemia. Hopefully a hemoglobin or hematocrit was also drawn.

Other causes of artifactual hyperkalemia during venipuncture include too tight a tourniquet, and repeated fist clinching. Thrombocytosis (platelets >500,000) can cause high potassium in vitro. A low serum potassium is always real, due to diuretics, G-I losses, or obscure conditions requiring work-up.

The main clinical dilemma occurs when an incidentally-discovered high potassium is >6.0 mEq/L, but not so high as to be obviously spurious. If the patient is on an ACE-Inhibitor, stop it. Beta-blockers only increase potassium around 0.5 mEq, so would be an unlikely culprit except in the context of renal disease.

Nephrology is so used to seeing a K+ of 6.0 that they hardly flinch, but we in primary care are pretty much obliged to call the patient in for a repeat, & possibly an EKG to rule-out peaked T-waves (a sine qua non of life-threatening hyperkalemia).


Laboratory measurements of sodium tend to be accurate. Very high triglyceridemia may cause an artifactual hyponatremia, as can high serum proteins in conditions like multiple myeloma. Uncontrolled diabetes (sugars >400) may modestly lower serum sodium by leaching water out of cells.

Work-up of sodium abnormalities invariably involves measurement of serum osmolality as well as urine chemistries. The only short-cut to diagnosis occurs in hyponatremic patients on thiazide diuretics — stop the drug & repeat the sodium.


Serum bicarb measurements from venous blood are only useful in the context of known electrolyte disturbances. If you’re really concerned about a patient’s acid-base status, you need arterial blood gases. An abnormal serum bicarb may suggest the need for this if the clinical context is suggestive.

I had an HIV patient with severe lactic acidosis due to an antiretroviral medication, and the only lab abnormality was a low bicarb. But she was clearly ill — vomiting & weight loss. A low bicarb in a patient with very high sugar may suggest ketoacidosis (which may well have decompensated by the time results are back). Other than such situations, an isolated abnormal bicarb in an asymptomatic patient can simply be repeated.



Since the kidney filters creatinine at a very steady & consistent rate, changes in serum creatinine level are invariably due to changes in renal function. However, emaciated patients with minimal muscle mass may have false-low values. Conversely, the muscle-bound weight-lifter may test false-high (similarly for large persons whose weight is disproportionately lean muscle).

A recently-consumed meal with lots of cooked meat can raise the creatinine as much as 1 mg/dL for several hours. Trimethoprim (in Septra®, Bactrim®, etc.) and Cimetidine can also cause false highs.

But aside from these situations, a rise in serum creatinine indicates a fall in glomerular filtration rate (GFR). In early renal insufficiency, small rises are significant; in frank renal failure, large rises are less important.

Personally, I only look at serum creatinines, not the “eGFR” values calculated by the lab. This may be a function of my age (“eGFR” calculations came out relatively recently), but also because they sound awfully scientific without having the patient’s weight factored in (much less if the weight is fat or lean).

A new rise in serum creatinine can usually just be repeated.  Any obvious causes like NSAIDs should be addressed.  A urinalysis is useful to check for abnormal sediment suggestive of intrinsic renal disease, and for possible UTI.

ACE-Inhibitors are tricky, since they are renal-protective in patients with proteinuria (e.g. diabetics), but can also cause renal insufficiency.  I often stop them if the creatinine rises, see if it then drops down, & then rechallenge the ACE-I repeating the creatinine in 5-7 days.

Whenever the creatinine rises, a BUN can be helpful.

Blood Urea Nitrogen (BUN)

This is primarily useful for interpreting the creatinine, and a few other clinical situations:

  • If BUN rises disproportionately to the Creatinine, you’re probably dealing with “prerenal” disease (see below)
  • The BUN rises with G-I bleeds, upper more than lower. So bad epigastric pain with a rise in BUN might be significant. Steroids also bump the BUN.
  • The BUN is disproportionately low in cirrhosis

The normal BUN-to-Creatinine ratio is 10-15 to 1, meaning that if a “normal” creatinine is 1.0 mg/dL, then the normal BUN is 10-15 mg/dL. So if the BUN rises disproportionately, it’s due to a “prerenal” problem before the blood enters the kidney (poor renal perfusion). This could be dehydration, heart failure, or any cause of volume loss.

However, the converse doesn’t hold water (pun); i.e. a normal BUN-to-Creatinine ratio doesn’t rule anything in or out, thus is simply not helpful.


Transaminases (ALT & AST)

The most important thing to realize is that the degree of transaminase elevation has nothing to do with the degree of liver injury. I had a patient with ALT reported at >10,000; it was benign Hep A.

What matters is the Prothrombin Time. Always order this in a patient with acute hepatitis. An INR ≤1.3 is normal. If 1.4 or 1.5 it’s equivocal. Anything 1.6 or higher may be heading for transplant.

An elevated ALT & AST imply something going on in the liver. However, they are also muscle enzymes, and will rise with muscle damage. An significantly elevated CPK might help confirm this.

With liver disease, the ALT is usually more elevated than the AST. A reverse of this normal ration suggests alcohol might be a cause.

For an in-depth discussion, see our topics Acute Hepatitis and Chronic Hepatitis.

Alkaline Phosphatase

An elevated Alk. Phos. can be due to liver disease, bone disease, placental production (2nd & 3rd trimesters), or intestinal activity (post-prandial). Rule out the last 2 conditions by a) eyeballing for a gravid uterus, and b) repeating the test fasting.

To distinguish liver from bone — if the ALT & AST are elevated, it’s liver disease. If they’re normal, order a 5´-nucleotidase [pronounced “5-prime”] or a gamma glutamyl transpeptidase (GGT). If either is elevated to the same extent as the Alk. Phos., you’re dealing with liver disease. If these are normal, investigate for bone disorders.

If transaminases are disproportionately elevated compared to the Alk Phos, it’s probably liver disease. If the Alk Phos is more impressive, it’s likely a cholestatic disorder. Get an ultrasound, but also order an Antimitochondrial Antibody (AMA), which is highly sensitive & specific for Primary Biliary Cirrhosis. This rule isn’t absolute, however. I’ll never forget my patient with very high ALT & AST, a modest increase in Alk Phos, who indeed had gallstones. [not fair]

If the AMA and ultrasound are both negative, you might as well rule out liver diseases, since sometimes they don’t follow the transaminase-to-AlkPhos rules. But you’ll probably have to send to G-I for an ERCP (or order an MRCP) to rule out a mass or other rare disorder. See the final section of our topic Chronic Hepatitis.


A decrease in serum albumin usually suggests cirrhosis. It’s considered a marker of hepatic “synthetic function” along with the Prothrombin Time; if the liver is unable to synthesize these proteins, it’s been compromised enough in its overall function as well. In acute liver failure, the Protime drops first, so a victim of mushroom poisoning might die with a normal albumin.

However, the serum albumin is also a “negative acute-phase reactant.” Just like the Sed Rate or CRP rise in response to inflammation, the albumin can fall (with no hepatic implications at all). Once the acute situation has resolved, the albumin returns to baseline.

As such, if you see an unusually low albumin in a patient without other suggestion of liver disease, draw a Sed Rate and/or CRP just to see.


Bilirubin may be Direct (conjugated) or Indirect (unconjugated). The difference between “Direct” and “Conjugated,” is that the way to measure physiologic Conjugated Bilirubin is by laboratory method that is called “Direct.”

Laboratories only routinely measure the Total & Direct Bili. Subtracting the latter from the former gives you the Indirect. Indirect Bilirubin can be measured on its own, but that’s more complex (read, “expensive”), & not part of a routine panel.

Jaundice is usually detectable when the bilirubin is >4 mg/dL. If you notice an elevation in someone you didn’t realize was jaundiced, go back & look at the sclera again.

High Bilirubin can be due to liver disease, biliary disease, or hemolysis. Hemolysis elevates the Indirect Bili, though not usually much over 5 mg/dL. Liver & biliary disorders elevate both, but especially the Direct. To distinguish, as noted above, if the Alk Phos is disproportionately increased compared to transaminases, it’s probably biliary tract, and visa versa. But not always.

The most ominous case of hyperbilirubinemia in adults is “Painless Jaundice” — turning yellow without any other symptoms whatsoever (not even malaise, anorexia, or nausea). It’s invariably a rapidly-metastasizing biliary tract or pancreatic cancer.

But then there’s Gilbert’s Syndrome, pronounced as in the French (Zheel-BAEH). It’s an inherited inability to conjugate bilirubin, leading to a high Total & Indirect Bili. All other Liver Function Tests and the CBC are stone normal; indeed, such a finding makes the diagnosis.  Patients’ eyes might look a little yellow, but nothing more — the condition is curious, but harmless. If you don’t like speaking French, it’s also called Meulengracht disease.

Next posting we’ll discuss the Glucose, Calcium, serum Proteins, and some other common chemistries not part of the Comprehensive Metabolic Panel.


2 responses to “Laboratory Tests – 2

  1. Thank you! This was very interesting.

  2. Good way of explaining, and fastidious paragraph to get information about my presentation subject,
    which i am going to present in academy.

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