Pancreatitis;

“My patient with severe Crohn’s disease is found to have an elevated serum lipase without other supportive evidence of pancreatitis. What other sources of elevated lipase should I consider?” 

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , Leave a comment

Over 20 different conditions have been linked to elevated serum lipase levels or hyperlipasemia associated with conditions other than pancreatitis. The most common causes are sepsis and acute kidney injury, but less common causes include gastrointestinal bleeding, liver disease, and type 2 diabetes mellitus, and inflammatory bowel disease.1   More specifically, up to 9% of patients with Crohn’s disease may have hyperlipasemia, often associated with a more extensive and active disease.2  

Recall that hyperlipasemia is one of the hallmarks of acute pancreatitis (serum lipase greater than 3-5x the upper limit of normal) but, as noted above, it is not 100% specific for this condition.  Although pancreatic tissue has a 50-to-100-fold greater lipase activity than other organs in the gastrointestinal tract,3 serum amylase may also be elevated in diseases involving salivary glands, stomach, heart, skeletal muscle, white and brown adipose tissue, and even the brain.1 This finding should come as no surprise since, as an enzyme, lipase metabolizes triglycerides into glycerol and free fatty acids and plays a key role in the metabolism and transport of lipids into peripheral tissues. 4   

Last, despite potential extra-pancreatic sources, serum lipase is still preferred over amylase in diagnosing pancreatitis due to its higher specificity and sensitivity. 5  

Bonus Pearl: Did you know that increased intracranial pressure, including intracerebral hemorrhage, edema, and tumors may also be associated with elevated serum lipase levels? 6 

Contributed by Charles Hurth, D.O., Mercy Hospital, St. Louis, Missouri

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References: 

  1. Feher KE, Tornai D, Vitalis Z, Davida L, Sipeki N, Papp M. Non-pancreatic hyperlipasemia: A puzzling clinical entity. World J Gastroenterol. 2024 May 21;30(19):2538-2552. doi: 10.3748/v30.i19.2538. PMID: 38817657; PMCID: PMC11135416. https://pmc.ncbi.nlm.nih.gov/articles/PMC11135416/#B33  
  2. Heikius B, Niemelä S, Lehtola J, Karttunen TJ. Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease. Am J Gastroenterol. 1999 Apr;94(4):1062-9. doi: 10.1111/j.1572-0241.1999.x. PMID: 10201484. https://pubmed.ncbi.nlm.nih.gov/10201484/ 
  3. Tetrault GA. Lipase activity in serum measured with Ektachem is often increased in nonpancreatic disorders. Clin Chem. 1991 Mar;37(3):447-51. PMID: 1706233. https://pubmed.ncbi.nlm.nih.gov/1706233/
  4. Wang H, Eckel RH. Lipoprotein lipase in the brain and nervous system. Annu Rev Nutr. 2012 Aug 21;32:147-60. doi: 10.1146/annurev-nutr-071811-150703. Epub 2012 Apr 23. PMID: 22540257; PMCID: PMC4065112. https://pmc.ncbi.nlm.nih.gov/articles/PMC4065112/
  5. Tenner S, Vege SS, Sheth SG, Sauer B, Yang A, Conwell DL, Yadlapati RH, Gardner TB. American College of Gastroenterology Guidelines: Management of Acute Pancreatitis. Am J Gastroenterol. 2024 Mar 1;119(3):419-437. doi: 10.14309/ajg.0000000000002645. Epub 2023 Nov 7. PMID: 38857482. https://pubmed.ncbi.nlm.nih.gov/38857482/
  6. Larson GM, Koch S, O’Dorisio TM, Osadchey B, McGraw P, Richardson JD. Gastric response to severe head injury. Am J Surg. 1984 Jan;147(1):97-105. doi: 10.1016/0002-9610(84)90041-2. PMID: 6691557. https://pubmed.ncbi.nlm.nih.gov/6691557/

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

“My patient with severe Crohn’s disease is found to have an elevated serum lipase without other supportive evidence of pancreatitis. What other sources of elevated lipase should I consider?” 

Is there any evidence that proton pump inhibitors (PPIs) benefit patients with acute pancreatitis?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Despite their widespread use, there is no firm evidence that PPIs should be routinely prescribed in the treatment of acute pancreatitis (AP).1   In fact, current guidelines do not include the use of PPIs as standard therapy in  AP. 1-3

Although a 2023 systematic review and meta-analysis involving 6 randomized controlled trials and 3 cohort studies of patients with AP found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI, no significant difference in the rates of 7-day mortality, length of hospital stay, or acute respiratory distress syndrome was found when compared to control groups.3

Theoretically, PPIs may improve the course of AP through reduction in the incidence of stress-related upper GI hemorrhagic complications.  However, the incidence of such complications in AP is quite low, ranging from 1.2% to 14.5%, with great majority of cases (>85%) unrelated to peptic ulcer disease. 3,4  These findings may help explain why it has been difficult to show any benefit for use of PPIs in reducing the incidence of GI bleed in AP.3,5

Similarly, although PPIs have been shown to reduce secretin-stimulated bicarbonate secretion by the pancreas, the clinical significance of this finding in the overall course of AP—except perhaps a lower risk of pseudocysts—remains unclear.3 Parenthetically, experimental studies have reported contradictory results regarding the inhibition of pancreatic enzyme production by PPIs,  with omeprazole failing to suppress amylase release in isolated pancreatic acini while pantoprazole showing reduced amylase secretion in rats.3

It is also unclear how the reported anti-inflammatory effects of PPIs may benefit the clinical course of AP.3,6 What is clear is that any potential benefits of PPIs in AP should be weighed against their potential adverse effects, including the risk of nosocomial pneumonia, Clostridiodes difficile infection, and spontaneous bacterial peritonitis.7,8 

Bonus Pearl: Did you know that PPIs may not only inhibit acid production by gastric parietal cells but also interfere with bactericidal activity of neutrophils?  One potential mechanism is interference with proton pump-dependent H202 generation within lysosomes necessary to create a highly acidic and bactericidal environment. 9  Fascinating!

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References

  1. Arvanitakis M, Dumonceau JM, Albert J, et al. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guideline. Endoscopy 2018; 50:524-46. Endoscopic management of acute necrotizing pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) evidence-based multidisciplinary guideline – European Society of Gastrointestinal Endoscopy (ESGE)
  2. Crocket SD, Wani S, Gardner TB, et al. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology 2018;154:1096-1101. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis (gastrojournal.org)
  3. Horvath IL, Bunduc S, Hanko B , et al. No evidence for the benefit of PPIs in the treatment of acute pancreatitis: a systematic review and meta-analysis. Scientific Reports 2023;13:2791. https://doi.org/10.1038/s41598-023-29939-S
  4. Rana SS, Sharma V, Bhasin Dk, et al. Gastrointestinal bleeding in acute pancreatitis: etiology, clinical features, risk factors and outcome. Tropical Gastroenterology 2015;36:31-35. http://www.tropicalgastro.com/articles/36/1/gastrointestinal-bleeding-in-acute.html
  5. Demcsak A, Soos A, Kincses L, et al. Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis-An international cohort study. Pancreatology 2020;20:1323-31.lyso https://www.sciencedirect.com/science/article/pii/S142439032030658X?via%3Dihub
  6. Hackert T, Tudor S, Felix K, et al. Effects of pantoprazole in experimental acute pancreatitis. Comparative Study 2010;8:551-7. https://pubmed.ncbi.nlm.nih.gov/20851132/
  7. Elzouki AB, Neffati N, Rasoul FA, et al. Increased risk of spontaneous bacterial peritonitis in cirrhotic patients using proton pump inhibitors. GE Port J Gastroenterol 2019; 26:83-89. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454390/#:~:text=The%20result%20showed%20that%20PPI,medical%20literature%20confirm%20this%20association.
  8. Yibirin M, De Oliveira D, Valera R, et al. Cureus 2021;13:e12759/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887997/#:~:text=The%20most%20likely%20explanation%20for,incidence%20of%20pneumonia%20%5B2%5D
  9. Ozatik O, Ozatik EY, Tesen Y, et al. Research into the effect of proton pump inhibitors on lungs and leukocytes. Turk J Gastroenterol 2021;32:1003-1011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975296/

 

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Is there any evidence that proton pump inhibitors (PPIs) benefit patients with acute pancreatitis?

My patient with Covid-19 and abdominal pain has an elevated lipase. Is there a connection between Covid-19 and acute pancreatitis?

FA Manian MD, MPH, , , , , , Leave a comment

Acute pancreatitis as a complication of Covid-19 is infrequent.1 Despite reports of elevated amylase/lipase and/or acute pancreatitis in some patients with Covid-19,2 the exact role that SARS-CoV-2 plays in causing acute pancreatitis is unclear at this time.

A retrospective study of over 11,000 hospitalized patients with Covid-19 in the U.S. found a point prevalence of acute pancreatitis of only 0.27%,3 while another retrospective study of Covid-19 patients seen in Spanish emergency rooms reported acute pancreatitis in only 0.07% of cases.4 Of interest, in the latter study, Covid-19 was associated with lower frequency of acute pancreatitis. Further adding to the controversy on the causative role of Covid-19 is lack of an observed increase in the incidence of acute pancreatitis during Covid-19 pandemic. 1

An earlier study from China reported mild elevation (<3x upper limits of normal) of amylase and/or lipase in 17% of patients with Covid-19 pneumonia, none of whom had abdominal pain. 5

The temporal relationship between Covid-19 and acute pancreatitis has varied from abdominal symptoms at the onset of Covid-19 symptoms to days after diagnosis of Covid-19? 1

Despite these disparate findings, Covid-19 related acute pancreatitis or pancreatic injury is plausible. Pancreatic ductal, acinar and islet cells express ACE2, an important receptor for SARS-CoV-2.1 Infection in the GI tract (virus can easily be found in the stool) may potentially spread from the duodenal epithelium to the pancreatic duct and the pancreatic parenchyma itself. Immune-mediated inflammatory response or endotheliitis caused by SARS-CoV-2 may also potentially explain reports of pancreatic injury in Covid-19. 1,2

Bonus Pearl: Did you know that SARS-CoV-2 has been found in pancreatic tissue of some patients who succumbed to Covid-19 and has been shown to infect human pancreatic beta cells in-vitro.6  Perhaps we should be on the lookout for diabetes as a consequence of Covid-19 as well!

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 References

  1. De-Madaria E, Capurso G. Covid-19 and acute pancreatitis: examining the causality. Nature Reviews Gastroenterol Hepatol 2021;18: 3-4. https://www.nature.com/articles/s41575-020-00389-y
  2. Kandasamy S. An unusual presentation of Covid-19: acute pancreatitis. Ann Hepatobiliary Pancreat Surg 2020;24:539-41. https://synapse.koreamed.org/upload/SynapseXML/2110ahbps/pdf/AHBPS-24-539.pdf
  3. Inamdar S, Benias PC, Liu Y, et al. Prevalence, risk factors, and outcomes of hospitalized patients with coronavirus disease 2019 presenting as acute pancreatitis. Gastroenterol 2020;159:2226-28. https://www.gastrojournal.org/article/S0016-5085(20)35115-5/pdf
  4. Miro O, Llorens P, Jimenez S, et al. Frequency of five unusual presentations in patients with Covid-19: results of the UMC-19-S. Epidemiol Infect 2020;148:e189. https://pubmed.ncbi.nlm.nih.gov/32843127/
  5. Wang F, Wang H, Fan J, et al. Pancreatic injury patterns in patients with coronavirus disease 19 pneumonia. Gastroenterology 2020;159:367-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118654/
  6. Wu C-T, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment. Cell Metab 2021 May 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130512/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient with Covid-19 and abdominal pain has an elevated lipase. Is there a connection between Covid-19 and acute pancreatitis?

My elderly patient has a WBC count of 60,000 without obvious hematologic malignancy.  How likely is it that his leukocytosis is related to an infection?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Although extremely high WBC count in the absence of myeloproliferative disease may be associated with solid tumors and other causes, infections are often the most common cause of leukemoid reaction (LR), including tuberculosis, Clostridiodes difficile colitis, shigellosis, salmonellosis, pneumonia, abscesses, as well as  parasitic infections (eg, malaria), fungal infections (mucormycosis), and viral diseases (eg, HIV, EBV, Chickungunya fever).1-4   

In a study of 173 hospitalized patients (mean age 69 y) with leukemoid reaction (defined in this study as WBC ≥30,000/µl), infection was the most common cause of LR (48%), followed by tissue ischemia/stress (28%), inflammation (eg, pancreatitis, diverticulitis without perforation) and obstetric diagnoses (7% each) and malignant tumor (5%).1 

In the same study, the most common infections were “sepsis”, pneumonia and urinary tract infections.  Bacteremia was documented in 13%, while Clostridiodes difficile toxin assay was positive in 7% of patients.  The highest WBC counts were observed in patients with either a positive blood culture or positive C. difficile toxin.  In-hospital mortality rate was very high at 62%.

Similarly, in a study involving 105 hospitalized patients, the most common cause was infection, followed by malignancy and other causes. 2 In a smaller study of 25 patients with “extreme” leukocytosis (defined as WBC ≥50,000/µl) infection was considered the cause in 52% and malignancy in 44% of patients; about one-third were bacteremic (eg, Pseudomonas sp, Streptococcus pneumoniae, E. coli).3

Bonus Pearl: Did you know that besides infections and malignancy, drugs (eg, corticosteroids, epinephrine) and ingestion of ethylene glycol have also been associated with LR? 1,3,4

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References

  1. Potasman I, Grupper M. Leukemoid reaction:Spectrum and prognosis of 173 adult patients. Clin Infect Dis 2013;57:e177-81. https://pubmed.ncbi.nlm.nih.gov/23994818/
  2. Portich JP, Faulhaber GAM. Leudemoid reaction: A 21st-century study. https://pubmed.ncbi.nlm.nih.gov/31765058/
  3. Halkes CJM, Dijstelbloem HM, Eelman Rooda SJ, et al. Extreme leucocytosis: not always leukaemia. The Netherlands J Med 2007;65:248-51. https://pubmed.ncbi.nlm.nih.gov/17656811/
  4. Kumar P, Charaniya R, Sahoo R, et al. Leukemoid reaction in Chickungunya fever. J Clin Diagn Res 2016;10:OD05-OD06. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948452/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My elderly patient has a WBC count of 60,000 without obvious hematologic malignancy.  How likely is it that his leukocytosis is related to an infection?

Why might Lactated Ringer’s (LR) solution be preferred over normal saline (NS) for fluid resuscitation in acute pancreatitis?

FA Manian MD, MPH, , , , , , Leave a comment

Although the data is limited, fluid resuscitation with lactated Ringer’s (LR) solution in acute pancreatitis has been associated with lower risk of persistent systemic inflammatory response syndrome (SIRS) compared to normal saline (NS),  with an additional trend toward lower mortality.1-3

A 2018 meta-analysis of 3 randomized-controlled trials (RCTs) and 2 retrospective studies involving 428 patients found a significantly lower odds of developing SIRS at 24 hours (OR 0.38, CI 0.15-0.98).   Mortality was also lower in the LR group (OR 0.61, 95% CI 0.28-1.29), though it did not reach statistical significance. 1

A small 2011 RCT was the first to suggest the “protective” effect of LR in acute pancreatitis, reporting significant reduction in the prevalence of SIRS after 24 hours when compared to NS (84% vs 0%);  patients on LR also had a significantly lower C-reactive protein (CRP) (104 mg/L vs 51.4 mg/L) at 24 hours. 2   Significantly lower CRP levels were also reported at 48 and 72 hours when LR was compared to NS in another RCT in acute pancreatitis.3

As for potential mechanisms for the observed beneficial effects of LR on the pancreatic tissue in acute pancreatitis, hyperchloremic metabolic acidosis (with its attendant low extracellular pH) often seen in large volume NS resuscitation was initially thought to contribute to pancreatic injury.2  A more plausible explanation, however, may relate to the direct anti-inflammatory effect of lactate itself.  Of interest, lactate has been shown to inhibit macrophage induction invitro 4  and suppress innate immunity in experimental models of pancreatitis. 3 Who would have guessed!

Bonus Pearl: Did you know that Ringer’s solution gets its name from Sydney Ringer, a 19th century physician who demonstrated the importance of salts of sodium, potassium, calcium and chloride in precise proportions for cellular function?  LR solution was actually concocted in the 1930s by a St. Louis pediatrician, Alexis Hartmann, and was also known as the “Hartmann’s solution”. 4

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References

  1. Iqbal U, Anwar H, Scribani M. Ringer’s lactate versus normal saline in acute pancreatitis: A systematic review and meta-analysis. J Dig Dis 208;19:335-341. https://onlinelibrary.wiley.com/doi/epdf/10.1111/1751-2980.12606
  2. Wu BU, Hwang JQ, Gardner TH, et al. Clin Gastroenterol Hepatol 2011;9:710-17. https://www.cghjournal.org/article/S1542-3565(11)00454-X/abstract
  3. de-Madaria E, Herrera-Marante I, Gonzalez-Camacho V, et al. Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial. UEG J 2017;6:63-72. file:///C:/Users/manifa/OneDrive%20-%20Mercy%20Online/pancreatitis%20LR2spain.pdf
  4. Lee JA. Sydney Ringer (1834-1910) and Alexis Hartmann (1898-1964). Anaesthesia 1981;36:1115-21. https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.1981.tb08698.x

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Why might Lactated Ringer’s (LR) solution be preferred over normal saline (NS) for fluid resuscitation in acute pancreatitis?

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?

FA Manian MD, MPH, , , , , , , , Leave a comment

You may have to!  That’s because patients with DM due to pancreatic disease (also known as “pancreatogenic [Type 3C] diabetes”) tend to have more labile blood glucoses with particular predisposition to severe hypoglycemic episodes due to the impairment of glucagon production by pancreatic alpha-cells. 1-3

This observation dates back to a 1977 study where a high rate of hypoglycemic episodes was found among 59 patients with chronic pancreatitis (most with insulin-dependent DM), including 3 deaths and 2 suffering from severe brain damage following hypoglycemic coma. Interestingly, low basal glucagon levels were found in the latter patients, supporting impairment in glucagon synthesis. Of note, while hypoglycemia is a serious problem in these patients, they are not spared from complications of chronic hyperglycemia, including retinopathy and kidney disease.2

As for the blood glucose management in type 3C DM, since the principle endocrine defect is insulin deficiency, insulin therapy is preferred for most patients, particularly those who are acutely ill or are hospitalized. For otherwise more stable patients with mild hyperglycemia, metformin is an ideal agent as it enhances hepatic insulin sensitivity without the risk of hypoglycemia. As a bonus, metformin may also decrease the risk of pancreatic cancer in chronic pancreatitis, based on observational studies. 4

Also, don’t forget that concurrent pancreatic exocrine insufficiency is common in patients with type 3C DM and requires oral pancreatic enzyme requirement with meals.

Fascinating Pearl: Did you know that in patients with type 3C DM, hyperglycemia is mediated not only by decreased production of insulin, but also by decreased synthesis of pancreatic polypeptide, a peptide that mediates hepatic insulin sensitivity and glucose production? 5

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References

  1. Linde, J, Nilsson LH, Barany FR. Diabetes and hypoglycemia in chronic pancreatitis. Scand J Gastroenterol. 2012;12, 369–373. https://www.ncbi.nlm.nih.gov/pubmed/867001
  2. Andersen D. The practical importance of recognizing pancreatogenic or type 3c diabetes. Diabetes Metab Res Rev. 2012;28:326-328. https://onlinelibrary.wiley.com/doi/abs/10.1002/dmrr.2285
  3. Cui YF, Andersen DK. Pancreatogenic diabetes: Special considerations for management. Pancreatology. 2011;11(3):279-294. doi:10.1159/000329188. https://jhu.pure.elsevier.com/en/publications/pancreatogenic-diabetes-special-considerations-for-management-4
  4. Evans J, Donnelly L, Emsley-Smith A. Metformin and reduced risk of cancer in diabetic patients. Br Med J. 2005;330:1304-1305. https://www.researchgate.net/publication/7888859_Metformin_and_reduced_risk_of_cancer_in_diabetic_patients
  5. Rabiee A. Gafiatsatos P, Salas-Carnillo R. Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patents on insulin pump therapy. J Diabetes Sci Technol 2011;5:1521-28.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262724/

Contributed by Hugo Torres, MD, MPH, Hospital Medicine Unit, Mass General Hospital, Boston, Massachusetts

I am admitting a patient with diabetes mellitus (DM) due to chronic pancreatitis. Should I manage her diabetes any differently than my other patients with DM?

Is it possible to have acute pancreatitis with normal serum lipase?

FA Manian MD, MPH, , , , , , Leave a comment

Yes! Although an elevated serum lipase has a negative predictive value of 94%-100% for acute pancreatitis (1), there are ample reports in the literature of patients with CT findings of pancreatitis in the presence of abdominal symptoms but with normal serum lipase and/or amylase (2,3).

A case series and review of literature of acute pancreatitis with normal lipase and amylase failed to reveal any specific risk factors for such observation (2). More specifically, the etiologies of acute pancreatitis in the reported cases have varied, including drug-induced, cholelithiasis, alcohol, hypertriglyceridemia, and postoperative causes.

But what accounts for this phenomenon? Many cases have been associated with the first bout of pancreatitis without evidence of pancreatic calcifications which makes the possibility of a “burned-out” pancreas without sufficient acinar cells to release lipase as a frequent cause unlikely. Other potential explanations for normal lipase in acute pancreatitis have included measurement of serum lipase at a very early phase of the disease before significant destruction of acinar cells has occurred (increases in 3-6 h, peaks at 24 h [4]) and more rapid renal clearance of serum lipase due to tubular dysfunction (2).

Of note, unlike amylase, lipase is totally reabsorbed by renal tubules under normal conditions (5). Thus, it’s conceivable that even a reversible tubular dysfunction may lead to increased clearance of serum lipase and potentially lower its levels.

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References
1. Ko K, Tello LC, Salt J. Acute pancreatitis with normal amylase and lipase. The Medicine Forum. 2011;11 Article 4. https://jdc.jefferson.edu/tmf/vol11/iss1/4/
2. Singh A, Shrestha M. Acute pancreatitis with normal amylase and lipase-an ED dilemma. Am J Emerg Med 2016;940.e5-940.e7. https://www.ncbi.nlm.nih.gov/pubmed/26521195
3. Limon O, Sahin E, Kantar FU, et al. A rare entity in ED: normal lipase level in acute pancreatitis. Turk J Emerg Med 2016;16:32-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882216/
4. Shah AM, Eddi R, Kothari ST, et al. Acute pancreatitis with normal serum lipase: a case series. J Pancreas (Online) 2010 July 5;11:369-72. PDF
5. Lott JA, Lu CJ. Lipase isoforms and amylase isoenzymes: assays and application in the diagnosis of acute pancreatitis. Clin Chem 1991;37:361-68. https://www.ncbi.nlm.nih.gov/pubmed/1706232

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is it possible to have acute pancreatitis with normal serum lipase?

Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

FA Manian MD, MPH, , , , , , Leave a comment

Depends on how high the serum levels are! Although the clearance of both amylase and lipase appears to be impaired in patients with significant renal insufficiency (eg,  creatinine clearance <50ml/min), serum levels greater than 2-4 times the upper limits of normal for these enzymes are still considered suggestive of pancreatitis in these patients1-3.

Interestingly, in hemodialysis patients, elevation of lipase may also be due to the lipolytic effect of heparin during this procedure.  That’s why obtaining serum lipase levels before, not after,  hemodialysis has been recommended4

Also fascinating is that most of the elevation of serum amylase in patients with significant renal insufficiency appears to be related to the elevation of salivary, not pancreatic, isoenzyme of amylase4.

Final fun fact: Did you know that at one time the diagnosis of pancreatitis was based on the activity of serum on starch (for amylase) and olive oil (for lipase)? 5

References

  1. Levitt MD, Rapoport M, Cooperband SR. The renal clearance of amylase in renal insufficiency, acute pancreatitis, and macroamylasemia. Ann Intern Med 1969;71:920-25. http://annals.org/aim/article/683643/renal-clearance-amylase-renal-insufficiency-acute-pancreatitis-macroamylasemia
  2. Collen MJ, Ansher AF, Chapman AB, et al. Serum amylase in patients with renal insufficiency and renal failure. Am J Gastroenterol 1990;85:1377-80. https://www.ncbi.nlm.nih.gov/pubmed/1699413
  3. Royce VL, Jensen DM, Corwin HL. Pancreatic enzymes in chronic renal failure. Arch Intern Med 1987;147:537-39. https://www.ncbi.nlm.nih.gov/pubmed/2435254
  4. Vaziri ND, Change D, Malekpour A, et al. Pancreatic enzymes in patients with end-stage renal disease maintained on hemodialysis. Am J Gastroenterol 1988;83:410-12. https://www.ncbi.nlm.nih.gov/pubmed/2450453
  5. Editorial. Pancreatic enzymes. N Engl J Med 1963;268:901-2. http://www.nejm.org/doi/pdf/10.1056/NEJM196304182681613
Is measurement of amylase and lipase useful in patients with renal insufficiency suspected of pancreatitis?

Should I order serum procalcitonin on my patient with suspected infection?

FA Manian MD, MPH, , , , , , , , , , , 2 Comments

Two things to ask before you order procalcitonin (PCT): 1. Will it impact patient management?; and 2. If so, will the result be available in a timely manner ie, within hours not days?

Whatever the result, PCT should always be interpreted in the context of the patient’s illness and other objective data. Not surprisingly then, as a “screening” test, PCT may be more useful in patients with low pre-test likelihood of having bacterial infection, not dissimilar to the use of D-dimer in patients with low pre-test probability of pulmonary embolism1.  

Several potential clinical uses of this biomarker have emerged in recent years,  including:1,2

  • Helping decide when to initiate antibiotics in patients with upper acute respiratory tract infections and bronchitis. A normal or low PCT supports viral infection.
  • Helping decide when to discontinue antibiotics (ie, when PCT normalizes) in community-acquired or ventilator-associated pneumonia.
  • Helping monitor patient progress with an expected drop in PCT of about 50% per day (half-life ~ 24 hrs) with effective therapy.

Few caveats…

  • PCT may be unremarkable in about a third of patients with bacteremia (especially due to less virulent bacteria, including many gram-positives)3.  
  • PCT levels are lowered by high-flux membrane hemodialysis, so check a baseline level before, not after, hemodialysis4.
  • Lastly, despite its higher specificity for bacterial infections compared to other biomarkers such as C-reactive protein, PCT may be elevated in a variety of non-infectious conditions, including pancreatitis, burns, pulmonary edema or aspiration, mesenteric infarction (ischemic bowel), cardiogenic shock, and hypotension during surgery2.

 

References:

  1. Schuetz P, Muller B, Chirst-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections (review). Evid-Based Child Health (A Cochrane Review Journal) 2013;8:4;1297-137. http://onlinelibrary.wiley.com/doi/10.1002/ebch.1927/pdf
  2. Gilbert GN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897488/pdf/0655-10.pdf
  3. Yan ST, Sun LC, Jia HB. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med 2017;35:779-83. https://www.ncbi.nlm.nih.gov/m/pubmed/27979420/#fft
  4. Grace E, Turner RM. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin Infect Dis 2014;59:1761-7. https://www.ncbi.nlm.nih.gov/pubmed/25228701
Should I order serum procalcitonin on my patient with suspected infection?