The gastrointestinal tract is involved in the absorption of nutrients such as fats, carbohydrates, proteins, vitamins, minerals, and trace elements. Malabsorption refers to impaired nutrient absorption at any point where nutrients are absorbed, and maldigestion refers to impaired nutrient digestion within the intestinal lumen or at the brush border. Although malabsorption and maldigestion differ, digestion and absorption are interdependent. Therefore, in much literature, the term “malabsorption” is used to refer to either process of this interdependence. For this discussion, the malabsorption syndromes addressed will primarily refer to those arising from dysfunction at the level of the small intestine, pancreas, or gallbladder.
Malabsorption can arise from any defect in the digestion/absorption process. These defects can result from an inherent disease of the mucosa, conditions that lead to acquired damage of the mucosa, congenital defects in the intestinal membrane transport systems, impaired absorption of specific nutrients, impaired GI motility (decreased peristalsis and stasis), disrupted bacterial flora, infection, or compromised blood flow or compromised lymphatics. The result is either a global impairment of absorption of all nutrients or specific nutrients.
Impaired nutrient absorption is often located somewhere along the small intestine since it provides a substantial surface area maximized by villi and microvilli and space within the lumen. Additional contributors to digestion and absorption are the gall bladder, pancreas, blood vessels, and lymphatics, which each have direct relationships with the small intestine. Digestion and absorption occur by a combination of mechanical mixing, enzyme synthesis, enzyme secretion, enzymatic activity, mucosal integrity, blood supply, intestinal motility, and a balanced microbial flora. Presenting symptoms of malabsorption syndromes overlap and some combination of diarrhea, steatorrhea, unintentional weight loss, developmental delay or skeletal deformities (in children), and, in many cases, observable anemia. Because of the various causes of malabsorption syndromes, treatment course and symptom management depend on etiology. This article will address digestion, absorption, and multiple malabsorption syndromes but will not be all-inclusive.
There are three stages of nutrient absorption: luminal, mucosal, postabsorptive. Malabsorption syndromes are categorized according to which of these three stages is or are affected.
Because malabsorption syndromes arise from dysfunction at any level of digestion or absorption, this discussion briefly addresses general components of digestion and absorption and gives examples of malabsorption diagnoses according to which nutrients are affected.
Fat malabsorption is one of the most common malabsorption syndromes, and it arises from defects in fat digestion and absorption. Lipid processing is emulsification, which is the process of suspending fat molecules in aqueous humor to expose lipid molecule surface areas to hydrolytic enzymes. Emulsification starts in the mouth via mastication and lingual lipase and continues with gastric mixing. Although lipid digestion begins in the mouth, approximately only 15% of ingested fat gets digested before reaching the duodenum, with the rest of the fat arriving in the duodenum intact before moving to the jejunum. The stomach and pancreas release lipolytic enzymes, and the majority of lipid absorption takes place in the proximal two-thirds of the jejunum (i.e., proximal small intestine). Additional fat solubilization is achieved by increasing intraluminal pH to 6.5 and mixing with bile salts released by the gallbladder to form micelles. The overall mixture of lipolytic products and other products of fat digestion aggregate into micelles or liposomes (larger aggregates than micelles). These specialized fat aggregates are the form in which fats can be absorbed. Diffusion, temporary integration into the lipid bilayer, and a multitude of transporters and co-transporters contribute to micelle and liposome-assisted fat absorption. Bile salts remain in the intestinal lumen and are reabsorbed in the terminal ileum and recycled via the enterohepatic circulation.
Causes of fat malabsorption: significant disruption of fat breakdown typically results in steatorrhea.
Carbohydrate digestion and absorption often refer to the starch, lactose, and sucrose of the human diet. Cellulose is not digestible in the human small intestine. Appropriate digestion into monosaccharides is necessary for adequate absorption. Carbohydrate digestion begins with salivary and pancreatic amylase. The resulting products get further processed at the microvillus membrane. Brush border enzymes then hydrolyze that carbohydrate mixture into monosaccharides. Monosaccharides can be absorbed passively or actively. Any remaining carbohydrates that are not absorbed (including the non-absorbable cellulose) get fermented in the colon (i.e., degraded by bacteria). When fatty acids get released as a result of bacterial fermentation, colonic epithelial cells can absorb them for energy. Symptoms of excessive bacterial fermentation in carbohydrate malabsorption include acidic stool, flatulence, and bloating.
Causes of carbohydrate malabsorption
Protein digestion and absorption begin as proteolysis in the stomach with proenzymes that become automatically activated at low pH levels (i.e., an acidic environment). The extent of proteolysis depends on pH levels, gastric motility for mixing, and other dietary constituents present during the process. For example, the duodenal and jejunal release of cholecystokinin (CCK) depends on the release of amino acids in the stomach. Amino acids stimulate the release of CCK and CCK stimulates the release of pancreatic enzymes. Additional release of amino acids occurs in the duodenum through the action of other proteases. After various levels of protein digestion by pancreatic enzymes, amino acids, dipeptides, and tripeptides are ready for absorption via brush border sodium-dependent amino acid co-transporters. These sodium-dependent amino acid co-transporters transport the products of proteolysis both passively and secondarily through their indirect use of energy from a sodium-potassium ATPase pump. Different classes of amino acid transporters exist and select out amino acids based on being neutral, basic, or acidic. Further selectivity exists for specific transport of dipeptides and tripeptides.
Causes of protein malabsorption
VITAMIN, MINERAL, AND TRACE ELEMENT MALABSOPRTION
Various intestinal transport mechanisms accomplish the absorption of vitamins, minerals, and trace elements. Dysfunction at any one of these levels results in malabsorption of that specific vitamin, mineral, trace element, or any nutrient dependant on them to be successfully absorbed. Deficiencies include but are not limited to deficiencies in vitamin B12, calcium iron, folate, vitamin D, magnesium, carotenoids, thiamin, copper, selenium, and more. The effects malabsorption of these vitamins, minerals, or trace elements depends on which is deficient and the degree to which they are deficient. Exploring the various mechanisms and covering the numerous etiologies are beyond the scope of this discussion.
Causes of malabsorption of vitamins, minerals, and trace elements
IMMUNODEFICIENCY AND HIV/AIDS-RELATED ENTEROPATHY
In some cases, malabsorption cannot readily be categorized into fat, carbohydrate, or micronutrient malabsorption when malabsorption is more global. The presentation may be diarrhea, weight, loss, and generalized malnutrition. This situation can present in immunodeficiency. Immunocompromised states accompanied by diarrhea often are due to secondary or opportunistic infections. These infections interfere with proper digestion and absorption processes. Infectious organisms include Giardia and Cryptosporidium. A more extensive discussion of the relationships between HIV/AIDS and other immunodeficient states is beyond the scope of this article but is mentioned for completeness.
CONGENITAL CAUSES OF CHRONIC DIARRHEA (not previously discussed)
Whether transient, curable, or permanent sequelae transpire, bacterial malabsorption is most often due to Giardia lamblia (giardiasis), Tropheryma whipplei, Cryptosporidium parvum (cryptosporidiosis), and the Phylum Microspora (microsporidiosis).
Malabsorption affects millions of people worldwide. The fact that malabsorption syndromes have multiple etiologies obscures the prevalence and incidence. However, some malabsorption syndromes can be estimated by discussing the epidemiology of subgroups.
Gluten-sensitive enteropathy (GSE) is present at its highest rates in 120-300 Europeans and North Americans. GSE can be found in parts of India and is rarest in those of Asain, Caribbean, and African descent. Tropical sprue is known for affecting residents of and visitors to Puerto Rico, the Caribbean, West Africa, northern South America, south-east Asia, and India.
The exact prevalence of pancreatic exocrine insufficiency is unknown in the general population but can be appreciated through its prevalence in specific subgroups with predisposing conditions. In those with chronic pancreatitis, the incidence is 85% in those with severe disease and 30% in those with mild disease and, again, 85% in newborns with cystic fibrosis. The prevalence ranges in diabetes with higher prevalence in diabetes type 1 (26% to 44%), in HIV/AIDS at 26% to 45%, in inoperable pancreatic cancer 50% to 100%, and with varying high incidence (19% to 98%) for surgeries (distal pancreatectomy, Whipple). Meanwhile, other populations show a lower prevalence (IBS, diabetes type 2).
The history and physical are invaluable when initiating the evaluation of malabsorption syndromes. A malabsorption syndrome should be suspected when a patient’s history includes but is not limited to ongoing or chronic diarrhea, unintentional weight loss despite normal nutrient intake, greasy, voluminous, foul-smelling stools that reportedly float. Additional components of the history may include flatulence, bloating, borborygmi. Abdominal pain might be reported but is less common in most malabsorption syndromes.
Key questions in the history and a focused physical exam help create a more targeted approach to the diagnosis of the patient’s condition. A thorough history boosts cost-effectiveness and saves time. For those patients whose malabsorption syndrome is affected by emotions, early treatment can start through interviews alone. The therapeutic benefit comes from the nurturing of the patient-doctor relationship by empowering the patient and positively impacting the patient’s self-esteem in the face of their malabsorption syndrome.
Questioning should include a review of systems, symptom duration, symptom timing, presence or absence of pain/pain radiation, location/location changes, intensity/intensity changes, known precipitating factors, associated symptoms (e.g., change in bowel habits/frequency), appearance of stool, whether or not the presenting symptoms have happened previously. Stool description could be of floating, pale, greasy stools, and a patient may report seeing oil droplets in the toilet, stool color, stool bulk, stool consistency, stool smell. Important additional questions include past medical history (e.g., peptic ulcer disease), family history (especially for systemic and gastrointestinal conditions), medications, surgeries, radiation exposure/treatments, caustic substance ingestion, allergies, and social history (e.g., smoking, drinking, recreational drug use past or present).
Physical exam should include a full abdominal examination and inspection of neighboring systems to consider differential diagnoses that could also account for the patient’s clinical presentation. Physical exam may yield findings of hyper/hypoactive bowel sounds, abdominal distention, abdominal tenderness (less common), pallor (suggests anemia), muscle wasting, abnormal deep tendon reflexes, skeletal deformities, rashes, cardiac arrhythmia, delayed growth (in infants and children), poor wound healing, ecchymosis, decreased visual acuity, peripheral neuropathy, auditory disturbances, or cognitive impairment.
Findings through the history and physical exam guide the next steps for evaluation.
Evaluation begins with a thorough history and physical, as discussed previously. Those findings will guide the next steps of assessment that consider options utilizing laboratory testing, imaging, visualization, and biopsies. Sometimes the cause of malabsorption is clear, and additional workup may be unnecessary or tailored more quickly to the specific diagnosis highest on the differential.
GENERAL EVALUATION FOR MALABSORPTION SYNDROMES:
When the history and physical raise suspicion for a malabsorption syndromes without strongly supporting a diagnosis that requires more specific testing, general testing may be started. Such an example is the non-specific symptoms of unintentional weight loss, ongoing diarrhea, or poor wound healing.
Laboratory testing is used to support the diagnosis but is not diagnostic.
Fecal tests: most sensitive for fat malabsorption syndromes
MORE SPECIFIC EVALUATION OF MALABSORPTION SYNDROMES:
When the history and physical make the diagnosis fairly clear, general evaluation is not necessary. Clinicians can select other modalities for assessment based on the suspected/most likely malabsorption diagnosis. Such examples include a patient’s history of recurrent pancreatitis and alcohol use or abdominal discomfort resolved with avoidance of gluten.
Jejunal aspirate culture:
Computed tomography (CT):
Magnetic resonance cholangiopancreatography (MRCP):
Magnetic resonance (MR) elastography:
Endoscopic retrograde cholangiopancreatography (ERCP):
Endoscopy with biopsy (indicated for diagnoses that require both visualization and biopsy):
Colonoscopies and biopsies:
Example of an evaluation for specific conditions:
Trials of eliminating certain types of foods or ingredients can be both diagnostic and therapeutic. This elimination testing is often useful in carbohydrate malabsorption syndromes such as lactose intolerance or fructose intolerance.
Treatment in the setting of malabsorption syndromes targets correcting deficiencies, treating the underlying cause, avoiding triggers (typically dietary), and treating symptoms (e,g often diarrhea).
Misdiagnosis or missed diagnosis of a malabsorption syndrome could cause harm or have no effect. Therefore, treatment should focus on treating the underlying cause, which depends on the diagnosis since malabsorption syndromes stem from their defects.
Treatment could be as conservative as dietary changes such as food avoidance or supplementation but could be as invasive as surgery (e.g., transplants, resections).
Diagnosis-driven management is also necessary for the relief of patient symptoms. For example, it is important to determine the cause of a patient’s diarrhea because incorrect treatment could exacerbate symptoms.
Secretory diarrhea, as can be seen following resection and results from excess bile acids in the colon, is treated differently than malabsorption diarrhea. Bile salt binders are indicated in secretory diarrhea to reduce osmotic load but would exacerbate diarrhea if malabsorption due to insufficient bile salts or bile salt dysfunction is the cause. In more transient malabsorption syndromes, antibiotics could be the cause of a patient’s diarrhea or the cure if due to a bacterial infectious process.
Therefore, malabsorption syndromes must be evaluated and diagnosed for successful management of the patient’s condition and symptoms indicated for the etiology.
Due to the overlapping symptoms between other malabsorption syndromes, they are differential diagnoses for one another. Differential diagnoses also include conditions that masquerade as abdominal pain such as pericarditis, myocardial infarction pulmonary infarction. These thoracic inflammatory events refer pain to the abdomen via the parietal diaphragmatic pleura or thoracic pleural.
Some differentials are specific to a malabsorption syndrome or presenting symptom:
Malabsorption syndromes typically are not life-threatening. However, the severity and duration of some malabsorption syndromes can be life-threatening or even fatal. Examples include severe malnutrition from prolonged pancreatic exocrine insufficiency, life-threatening electrolyte disturbances from prolonged, intractable diarrhea, and bowel perforation.
Meanwhile, other malabsorption syndromes such as lactose intolerance are unlikely to deteriorate a patient’s health significantly. That is partly due to disease progression and partly due to the efficacy of disease management (e.g., avoidance, supplementation, supportive care).
The complications that can arise from malabsorption and maldigestion are as numerous as the points at which these processes can be interrupted, delayed, or absent. When a malabsorption syndrome is severe enough, poorly controlled, or of long enough duration, complications can include (not a comprehensive list):
Teaching patients about their medical condition improves patient adherence to treatment plans. Therefore, medical professionals must discuss the patient’s signs, symptoms, treatment options, and goals for quality of life. This approach increases patient investment and fosters increased patient empowerment as it pertains to their role in their health even when challenged with unavoidable obstacles such as cost or home environment. Typically, a patient’s quality of life, especially in the face of a medical diagnosis, can be improved by discussing stress management. Whether the patient has the opportunity to discuss stress with individuals such as their primary care provider, a dietician, or a therapist, stress reduction has demonstrated improved patient outcomes and satisfaction.
Conditions such as lactose malabsorption and intolerance could fall prey to an insouciant approach due to its virtual impossibility of fatal outcomes. However, food intolerance has serious implications for the patient’s quality of life and, depending on the etiology, for the patient’s medical status. As health care providers, tremendous emphasis should be placed on the quality of life and not underestimate the negative impact on a patient when there lacks an immediate threat to our patient’s medical status. Furthermore, food intolerance is important because it can easily be the cause of IBS and other functional GI disorders. Additionally, investigating food intolerances and malabsorption syndromes can even improve cost-effectiveness through interventions as conservative as dietary therapy. In more intricate and complicated cases such as ultrashort bowel syndrome in infancy, caregivers endure multiple sleep interruptions at night due to pump alarms, perform toileting, administer stoma/gastrostomy bag care, and provide enteral tube feeding throughout the day, enhancing healthcare team outcomes becomes more readily apparent to any observer. Therefore, exemplary evaluation and management of malabsorption syndromes, like any medical condition, can reduce the burden of even caregivers, a critical component involved in patient outcomes.
Generally speaking, enhancing interprofessional health care team outcomes depend heavily on a loop that begins and ends with the patient. This approach means that the patient is part of the team, and management starts with enough patient involvement to present for a medical visit. Followed by the physician, nurse, or physician assistant’s appropriate clinical knowledge and skills. The history and physical then guide appropriate evaluation. At any time during patient management, the patient’s every point of contact plays a role in the patient’s outcome. The individuals include but are not limited to specialists (e,g. consults, referrals, radiologists, surgeons, therapists), lab technicians, phlebotomists, medical assistants, and patient transport services. The key is appreciating the impact team dynamics can have on patient outcomes, no matter how brief. Compassion remains necessary for a positive, motivating, productive relationship when interacting with the patient, especially when the realities of patient obstacles arise, such as those with transportation, insight, mental or physical capacity, symptom burden, psychological state, treatment adherence, or financial/economic status.
Patient encounters should include setting realistic goals, discussing realistic treatment options, and shared-decision making. Nursing staff should inquire at each visit regarding the progression of patient symptoms, compliance with management plans, and solicit questions from the patient. These behaviors with the maintenance of professional conduct increase the likelihood that the patient remains engaged in their health status, which is reflected in patient proactiveness, follow up, adherence to the treatment plan when home, and staying informed. When these take place to the best of the patient’s ability, the interprofessional team maximizes a patient’s outcome. [Level 5]
|||Konturek PC,Brzozowski T,Konturek SJ, Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2011 Dec; [PubMed PMID: 22314561]|
|||Owens SR,Greenson JK, The pathology of malabsorption: current concepts. Histopathology. 2007 Jan; [PubMed PMID: 17204022]|
|||Clark R,Johnson R, Malabsorption Syndromes. The Nursing clinics of North America. 2018 Sep; [PubMed PMID: 30100002]|
|||Goodman BE, Insights into digestion and absorption of major nutrients in humans. Advances in physiology education. 2010 Jun; [PubMed PMID: 20522896]|
|||Rinawi F,Iancu TC,Hartman C,Cohen H,Yarden-Bilavsky H,Lev MR,Shamir R, Fat malabsorption due to bile acid synthesis defect. The Israel Medical Association journal : IMAJ. 2015 Mar; [PubMed PMID: 25946774]|
|||Rowe K,Pankow J,Nehme F,Salyers W, Gastrointestinal Amyloidosis: Review of the Literature. Cureus. 2017 May 8; [PubMed PMID: 28611935]|
|||Shah R,John S, Cholestatic Jaundice (Cholestasis, Cholestatic Hepatitis) 2019 Jan; [PubMed PMID: 29489239]|
|||Fujimori S, What are the effects of proton pump inhibitors on the small intestine? World journal of gastroenterology. 2015 Jun 14; [PubMed PMID: 26078557]|
|||Othman MO,Harb D,Barkin JA, Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician. International journal of clinical practice. 2018 Feb; [PubMed PMID: 29405509]|
|||Mushtaq I,Cheema HA,Malik HS,Waheed N,Hashmi MA,Malik HS, Causes Of Chronic Non-Infectious Diarrhoea In Infants Less Than 6 Months Of Age: Rarely Recognized Entities. Journal of Ayub Medical College, Abbottabad : JAMC. 2017 Jan-Mar; [PubMed PMID: 28712180]|
|||Monstein HJ,Folkesson R, Phorbol 12-myristate-13-acetate (PMA) stimulates a differential expression of cholecystokinin (CCK) and c-fos mRNA in a human neuroblastoma cell line. FEBS letters. 1991 Nov 18; [PubMed PMID: 1720402]|
|||Fernández-Bañares F,Monzón H,Forné M, A short review of malabsorption and anemia. World journal of gastroenterology. 2009 Oct 7; [PubMed PMID: 19787827]|
|||Mazigh S,Yahiaoui S,Ben Rabeh R,Fetni I,Sammoud A, [Diagnosis and management of cow's protein milk allergy in infant]. La Tunisie medicale. 2015 Apr; [PubMed PMID: 26375735]|
|||Sherman R, Abdominal Pain 1990; [PubMed PMID: 21250252]|
|||Ferguson CM, An Overview of the Gastrointestinal System 1990; [PubMed PMID: 21250246]|
|||Matsuda S,Motosugi U,Kato R,Muraoka M,Suzuki Y,Sato M,Shindo K,Nakayama Y,Inoue T,Maekawa S,Sakamoto M,Enomoto N, Hepatic Amyloidosis with an Extremely High Stiffness Value on Magnetic Resonance Elastography. Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine. 2016 Jul 11; [PubMed PMID: 27001387]|
|||Dolmans RA,Boel CH,Lacle MM,Kusters JG, Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections. Clinical microbiology reviews. 2017 Apr; [PubMed PMID: 28298472]|
|||Hammi S,Berrani H,Benouchen T,Lamlami N,Elkhiyat I,Bourkadi JE, A primary intestinal lymphangiectasia hiding the diagnosis of pleural and pericardial tuberculosis: a clinical observation. The Pan African medical journal. 2017; [PubMed PMID: 28491220]|
|||Misselwitz B,Butter M,Verbeke K,Fox MR, Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management. Gut. 2019 Nov [PubMed PMID: 31427404]|
|||Batra A,Keys SC,Johnson MJ,Wheeler RA,Beattie RM, Epidemiology, management and outcome of ultrashort bowel syndrome in infancy. Archives of disease in childhood. Fetal and neonatal edition. 2017 Nov [PubMed PMID: 28866623]|
|||Lavallee DC,Chenok KE,Love RM,Petersen C,Holve E,Segal CD,Franklin PD, Incorporating Patient-Reported Outcomes Into Health Care To Engage Patients And Enhance Care. Health affairs (Project Hope). 2016 Apr [PubMed PMID: 27044954]|