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Pancreatic Exocrine Insufficiency

Maldigestion is a challenging presentation for clinicians as a plethora of concerns can be at play. One that seems to be commonly missed is pancreatic exocrine insufficiency or #PEI, which essentially is the reduction of pancreatic enzyme activity in the intestinal lumen below what is necessary for optimal digestion. It is unknown how many people actually suffer with this condition.



Challenging this diagnosis though, and its treatment, is the fact that a reduction in enzyme activity can happen yet be inadequate for diagnosis of insufficiency. Steatorrhea, or fatty stool, doesn't occur though until pancreatic lipase output is reduced to only 5 to 10 percent of normal output, so this should be a significant red flag. Testing though for pancreatic secretion may identify chronic pancreatitis but not necessarily indicate pancreatic insufficiency. Also making this a challenging diagnosis is that anything that may interrupt the proper chain of events required for normal digestion of ingested food by pancreatic enzymes may cause PEI, which may not be specific to the pancreas whatsoever. All these variables means pancreatic maldigestion is probably a better term.


Diseases of the pancreas such as Cystic Fibrosis, necrotizing acute pancreatitis, and chronic pancreatitis are the more common causes of PEI; however, it may also result from obstruction of the pancreatic duct system due to a tumor or stricture, or untreated #Celiac disease, Zollinger-Ellison syndrome, or Crohn's disease.


The presence of fatty acids, amino acids, and gastric acid in the duodenum is the most potent stimulator of exocrine pancreatic secretion. We also have natural reflexes that stimulate pancreatic secretion, as well as hormones that stimulate secretion. The inability to digest fats is the determining factor that causes the most important symptoms and clinical complications because lipase, the major lipolytic enzyme of the pancreatic juice, is the pancreatic digestive enzyme with the poorest stability in the gastrointestinal lumen.


The destruction of lipase is even more rapid when the pH is below 4, which is often the situation in chronic #pancreatitis, in which the buffering of gastric acid is insufficient due to low bicarbonate excretion by the pancreas. There is also very limited additional support for fat digestion, as there is for carbohydrates from the salivary amylase or gastric pepsinogen.


PEI is a major complication of chronic pancreatitis and should be considered in all these patients. The likeliness of PEI increases with disease duration, and approximately half of sufferers will have developed PEI by twelve years of disease onset. Sufferers of PEI not only suffer from impaired quality of life due to #steatorrhea, weight loss, abdominal discomfort and other PEI-related symptoms but they are also highly likely to develop deficiencies of micronutrients and lipid-soluble vitamins. Osteoporosis then becomes a concern. Early and accurate diagnosis is important.


Diagnosis of Pancreatic Exocrine Insufficiency


A three-day fecal fat quantification and determination of the coefficient of fat absorption is the gold standard for diagnosis of PEI. A major drawback however, of this testing is it being both cumbersome and unpleasant. The individual will be asked to keep a strict diet, with 100 grams of fat per day for five days, and to collect the complete volume of feces for three days. This is only available at a few specialized labs due to the complexity of this test. Several alternative methods are often favored.


Symptoms can vary depending on the degree and the underlying cause, but the classically picture is a patient presenting with foul-smelling, loose stools, weight loss, muscle wasting, and flatulence. Testing isn't typically necessary when chronic pancreatitis is ominous alongside the previously mentioned symptoms. A trial of pancreatic enzymes is recommended by several national societies when the clinical presentation is strongly suggestive of PEI. However, only relying on symptoms may lead to both over and under diagnosing. Each of these symptoms can be related to a number of other conditions, and PEI can also be present in the absence of overt steatorrhea.


Testing for malnutrition can also support diagnosis. Deficiencies in hemoglobin, albumin, prealbumin, apolipoproteins, total cholesterol, magnesium, lipid-soluble vitamins, retinol-binding protein, calcium, zinc, and selenium are common, while vitamin B12 and folate levels aren't necessarily associated with PEI. Elevated HbA1C may also be in the upper limits of normal. If these are normal, then PEI can be excluded.


Imaging can also be done. Ductal changes on endoscopic retrograde pancreatography, computerized tomography, and endoscopic ultrasound have also been associated with decreased exocrine pancreatic function. Several abnormalities based on specific criteria would assist in diagnosing PEI.


There is a breath test that measures the clinically most relevant end-effect of exocrine pancreatic function, the degradation of triglycerides. The C-mixed triglycerides (C-MTG) is preferable to tests that measure exocrine pancreatic secretion, such as the secretin test and the FE-1 assay, but for this test, it is necessary for the patient to ingest a small amount of C-marked triglycerides together with butter on a piece of toasted bread, after an overnight fast. In a healthy individual with normal lipase activity, C-triglycerides will be degraded in the intestinal lumen and C-marked fatty acids will then be absorbed. These fatty acids will in turn be metabolized in the liver, and CO2 can finally be measured in exhaled air. Subjects with PEI however, have decreased lipase activity which can be detected as a decreased recover of CO2 in exhaled air. The challenge though is many of these clients are avoiding dairy or gluten or wheat, and there is no real agreement on the optimal design of the test. A popular proposal though is to consider all values below 29 percent as pathologic which offers more than 90 percent sensitivity on detecting fat maldigestion.


There is the option of anchoring a large-bore tube down the throat into the gut and then aspirating the gastric juices after eating a standard meal to evaluate pancreatic exocrine function, but clients haven't really favored this option. There is also an endoscopic function test but might even the violation of the gut by these probes alter the effect of pancreatic enzymes in the gut themselves?


Fecal fat quantification and the C-MTG breath test really are the best options for accurate diagnosis, but even they aren't readily available. An algorithm has been created though to assist with diagnosis utilizing symptoms, routine blood tests, fecal elastase 1 (FE-1) from a spot fecal sample, and standard imaging. While incredibly helpful, it is only an estimation of the probability of PEI and it has not been scientifically validated.


Essentially this algorithm evaluates for clinical suspicious, then nutritional markers and fecal elastase are evaluated. If fecal elastase <15 then there is high probability of PEI; however, if results are 15-200 or accompanied with abnormal nutritional markers, then MDP dilation or calcifications on imaging become important to identify the potential for PEI. If fecal elastase is higher than 200 and a normal nutritional panel is identified, then there is low probability of PEI.


Treatment of Pancreatic Enzyme Insufficiency


The cornerstone of treatment for PEI is pancreatic enzyme replacement therapy, but also the cessation of both smoking and alcohol consumption. A dietary consult may prove helpful as the goal is to normalize digestion, alleviate PEI-related symptoms and to prevent malnutrition-related morbidity and mortality, as well as disease progression.


Finding the right dose of enzymes can prove challenging, but the goal is regulation of the #lipase units which is typically somewhere between 25K and 50K units per meal. If this is still not getting the desired results, then add a #PPI or supportive botanical, or even double the pancreatic enzymes. Eat small and frequent meals, take in a healthy fat ratio, and utilize a fat soluble vitamin. Do not skip the lifestyle changes; this is imperative. Nutritional markers should be monitored. Support groups or Wellbutrin may be helpful for addiction. Body composition should be monitored as well as symptoms of #maldigestion.


Keep in mind that historically a low fat diet has been recommended for those suffering with PEI because the idea was to reduce steatorrhea. This recommendation has been abandoned because it can clearly impact further weight loss and deficiencies of lipid-soluble vitamins. Optimizing pancreatic enzymes is really the goal, then supporting with the proton pump inhibitors if enzymes aren't relieving symptoms, and most PEI individuals will tolerate a normal fat diet. Small intestinal bacterial overgrowth would be another consideration if treatment isn't resolving symptoms.


Alcohol withdrawal can slow the deterioration of pancreatic exocrine function so effort in this regard is important. Smoking, of course, can contribute to pancreatic #cancer, acute pancreatitis, and chronic pancreatitis so working to rid this #addiction is equally important.


This really can be a challenge to identify, diagnose and manage. A trusting and compassionate relationship between client and practitioner is necessary to support the client through this difficult time. Misdiagnosis can be ongoing for decades and be truly devastating.


References

Lindkvist, B. (2013). Diagnosis and treatment of pancreatic exocrine insufficiency. World Journal of Gastroenterology, 19(42), 7258-7266.

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