Medical Concepts: Abdominal Pain Labs

A 40 year-old woman presents to your emergency department with a chief complaint of abdominal pain. Unfortunately, she does not speak English but an interpreter is being contacted. It is clear that she is in a lot of pain and she is not able to cooperate with your physical exam. Pain medication has been ordered and you are considering the workup that you need to get started. You wonder which investigations will be most helpful in determining the cause of this undifferentiated presentation.

The Question: Abdominal Pain Labs

Which laboratory investigations are useful in patients with undifferentiated acute abdominal pain?

The Big Picture: Sick or Not Sick?

The most important factor in the emergency department management of abdominal pain is the distinction between sick and not-so-sick patients. The c-reactive protein (CRP) and white blood cell count (WBC) are useful laboratory investigations.

CRP is correlated with the likelihood of serious pathology on abdominal CT scan [1] and hospital admission [2]. It is also associated with more urgent diagnoses [3].

Like the CRP, a high white blood cell count is associated with hospital admission and more urgent pathology [2,3]. The white blood cell count differential can also provide clues to the etiology of abdominal pain. Neutrophilia (>9×10⁹/L) combined with lymphopenia (<1.4×10⁹/L) and eosinopenia (<0.04×10⁹/L) is 95% specific, though insensitive, for an infectious or surgical cause for acute abdominal pain [4].

The combination of elevated CRP and white blood cell count should ring alarm bells. A patient with a CRP of greater than 50 mg/L and a WBC of greater than 15 has an 85% of having an urgent diagnosis [3]. Be warned that these tests are not sensitive. In other words, there are many things that don’t cause an elevated CRP or an elevated white blood cell count but are dangerous.

There is one other big picture test worth highlighting: All pre-menopausal women should have a urine or serum beta-HCG test. A negative pregnancy test rules out some life-threatening pathologies, and a positive one may mean a critical difference in subsequent management.

The Specifics on Abdominal Pain Labs

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How good are lab tests for pancreatitis?

The two abdo lab tests commonly used to rule in or rule out pancreatitis are serum lipase and serum amylase. Amylase is secreted both by the pancreas and the salivary glands, and lipase is only secreted by the pancreas, This may explain why the lipase is, statistically, the better test; elevated serum lipase is both more specific (95-99%) [5] and more sensitive (see below) than elevated serum amylase for acute pancreatitis. Ordering both tests doesn’t improve sensitivity or specificity over lipase alone. Some estimates of lipase sensitivity are as low as 67%, so a normal lipase doesn’t exclude pancreatitis with certainty.

Use serum amylase and lipase with caution in a patient with chronic pancreatitis. Some of these patients have chronically elevated levels, and it is important to interpret the results in the context of the patient’s baseline, if you know it.

How good are lab tests for biliary tract disease?

The classic lab findings of biliary tract disease vary with the pathology. Biliary colic, with obstruction limited to the gallbladder itself, typically has no abnormal lab findings. Leukocytosis is often seen in acute cholecystitis as the gallbladder becomes inflamed. Acute cholangitis, with obstruction of the biliary tract, classically shows elevated bilirubin levels due to impaired excretion; elevated alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) are also seen as they are released from damaged liver cells. Elevated AST and ALT are sometimes seen as well, but are not part of the classic “obstructive pattern”.

In practice, there aren’t great studies on the sensitivity and specificity of these tests. The authors of one review of diagnostic tests [6] found that bilirubin, AST/ALT, and alkaline phosphotase were not statistically useful tests for diagnosing acute cholecystitis. Only an elevated WBC was statistically significant, and this has very limited clinical use because it is so non-specific. Good data on the sensitivity and specificity of lab values for acute cholangitis are not available, but consider this diagnosis if there is elevated bilirubin, alkaline phosphatase, GGT, AST, or ALT in the setting of abdominal pain.

How good are lab tests for hepatic disease?

The most commonly used tests to look for hepatic injury are the transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Both are fairly sensitive tests for liver damage, but AST is found in non-hepatic tissue more than ALT and so is less specific [7]. Rises of up to 300 IU/L are non-specific, but levels above 1000 IU/L are most commonly due to viral hepatitis, toxin or drug induced hepatitis, or ischemic injury [7], though actual levels don’t have much prognostic significance.

While AST and ALT can give an idea of how much damage has been done, they don’t show how well the liver is functioning. For that, the INR is the most commonly used test. Clotting factor VII has a half-life of six hours, and falling serum levels if hepatic production is failing will show as a rising INR[7].

How good are lab tests for renal colic?

A urine dip and/or urinalysis is often ordered if renal colic is suspected. Among adult patients presenting with flank pain, blood on a urine dip has been estimated to have a positive predictive value of 54% and a negative predictive power of 66%[8]. In the same population, a cutoff of 5 RBCs per high power field on urinalysis has a 65% positive predictive value and 68% negative predictive value[8]. These tests may point you in the right direction, but they aren’t nearly specific enough to be relied on without a solid history suggestive of renal colic.

How good are lab tests for appendicitis?

In short, laboratory tests for appendicitis are not useful. Much of the traditional teaching about appendicitis has stressed the role of leukocytosis[9]. The literature, however, is equivocal. The authors of one large metaanalysis[10]found that higher white blood cell counts were indeed correlated with appendicitis, but as a single test it was of limited use. Very high values of leukocytosis (>15×10⁹) only had a positive likelihood ratio of 3.5, and low cut-off values (10×10⁹) had a negative likelihood ratio of 0.3. In other words, normal WBC values couldn’t exclude appendicitis, and high values could not confirm it. The combination of a normal WBC and a normal CRP may seem reassuring, but the use of these tests to rule out appendicitis has not been well established[10].

What about ALL the other causes of abdominal pain?

Besides the pancreas, gallbladder, liver, and ureter, the organs that might be causing acute addominal pain don’t have any organ-specific or pathology-specific lab test. There is a long and sobering list of pathologies that can cause abdominal pain with no specific lab findings: peptic ulcer disease (with or without perforation), gastritis, small bowel obstruction, acute mesenteric ischemia, diverticulitis, cecal volculus, ruptured abdominal aortic aneurism, pyelonephritis, pelvic inflammatory disease, ruptured ectopic pregnancy, inflammatory bowel disease … you get the idea.

Undifferentiated abdominal pain is a presentation where the history and physical exam are absolutely crucial, and laboratory tests are confirmatory. Some experts advise against the use of standard panels of “belly labs”[11], as there is no evidence they are useful for the undifferentiated patient, and may add diagnostic confusion. Instead, rely on your history, physical exam wherever possible.

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Back to the case

You go on a laboratory spree and send off the works: urinalysis (including beta HCG), CRP, lipase, bilirubin, AST, ALT, GGT, alkaline phosphatase, and the standard CBC, electrolytes, urea and creatinine. The labs come back normal except for a borderline white blood cell count at 10.5. In desperation, you send the patient for an abdominal ultrasound. The radiologist identifies acute cholecystitis. The patient has a laparoscopic cholecystectomy the next day, and recovers well.

The Bottom Line on abdominal pain labs

All pre-menopausal women should have a beta HCG test.
The white blood cell count and CRP are correlated with illness severity, but cannot be relied upon in isolation to rule in or out serious disease.
Elevated serum lipase is specific for pancreatitis, but not sensitive enough to rule it out conclusively.
Biliary colic and acute cholecystitis do not have sensitive or specific laboratory findings. The sensitivity and specificity of the classic laboratory findings of acute cholangitis haven’t been thoroughly studied.
Liver enzymes are reasonably sensitive and specific (especially ALT) for hepatic injury, but hepatic injury itself has a long differential diagnosis.
Hematuria is associated with renal colic, but is of limited usefulness in isolation.
The history and physical exam are key in determining the cause of acute undifferentiated abdominal pain.

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References

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Chi, C H, S C Shiesh, K W Chen, M H Wu, and X Z Lin. “C-Reactive Protein for the Evaluation of Acute Abdominal Pain.” The American Journal of Emergency Medicine 14, no. 3 (May 1996): 254–56. doi:10.1016/S0735-6757(96)90169-2.
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Trowbridge, Robert L, Nicole K Rutkowski, and Patient Page. “Does This Patient Have Acute Cholecystitis?” Journal of the American Medical Association 289, no. 1 (2003).
Pratt, Daniel S. “Evaluation of Liver Function.” In Harrison’s Principles of Internal Medicine., edited by Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, and Joseph Loscalzo, 19th editi. McGraw-Hill Education, 2015. http://accessmedicine.mhmedical.com.proxy.queensu.ca/book.aspx?bookid=1130.
Bove, P, D Kaplan, N Dalrymple, a T Rosenfield, M Verga, K Anderson, and R C Smith. “Reexamining the Value of Hematuria Testing in Patients with Acute Flank Pain.” The Journal of Urology 162, no. 3 Pt 1 (1999): 685–87. doi:10.1097/00005392-199909010-00013.
Pines, Jesse M., Christopher R. Carpenter, Ali S. Raja, and Jeremiah D. Schuur. Evidence-Based Emergency Care: Diagnostic Testing and Clinical Decision Rules. 2nd ed. Chichester, UK: John Wiley & Sons, Ltd., 2013.
Andersson, R. E. B. “Meta-Analysis of the Clinical and Laboratory Diagnosis of Appendicitis.” British Journal of Surgery 91, no. 1 (2004): 28–37. doi:10.1002/bjs.4464.
Salem, T A, R G Molloy, and P J O’Dwyer. “Prospective Study on the Role of C-Reactive Protein (CRP) in Patients with an Acute Abdomen.” Annals of the Royal College of Surgeons of England 89, no. 3 (April 2007): 233–37. doi:10.1308/003588407X168389.