The Medical Student Notebook—New Column!

| March 26, 2014

This column is written by medical students and is dedicated to reviewing the science behind obesity and bariatric surgery.

Lesson #1 explores topics in gastrointestinal physiology and discusses the implications of gastric bypass surgery for each subject.

Column Editor: Daniel B. Jones, MD, MS, FACS
Professor of Surgery, Harvard Medical School
Vice Chair, Beth Israel Deaconess Medical Center
Boston, Massachusetts

Featured Student: Kyle D. Checchi, MSc
Medical Student, Harvard Medical School, Boston, Massachusetts

This month: Lesson #1: Bariatric Physiology
Part 1: Bariatric Surgery and Vitamin B12   
by Kyle D. Checchi, MSc

Introduction
Gastroenterology is as important to understanding health and disease as cardiology, pulmonology, or endocrinology. Given the growing burden of disease related to obesity,[1] the importance of understanding gastrointestinal physiology will only continue to grow. As the only clinically effective treatment for refractory morbid obesity,[2] gastric bypass surgery represents an important topic: gastrointestinal physiology. Understanding gastrointestinal physiology and the changes that follow gastric bypass surgery will be important for explaining the success of our current gold-standard therapy, guiding long-term patient management, and refining current techniques, in addition to developing novel treatments.

The gastrointestinal tract features a highly specialized corridor and its associated solid organs. With its various segments adapted to particular functions of digestion and absorption, the gastrointestinal tract is comparable in its complexity to its physiologically esteemed counterpart, the nephron. In fact, the nephron and the gastrointestinal tract share many transporters and mechanisms of transporting molecules;[3] however, the gastrointestinal tract also regulates the hormonal balance of metabolism in the body and contains its own enteral nervous system in addition to its connections to the central nervous system.[4]

Bariatric surgery, specifically the popular Roux-en-Y gastric bypass procedure, rearranges the natural relationship of the gastrointestinal tract and fundamentally changes the way that that gastrointestinal structures interact with the nutrients they are responsible for processing and absorbing. Surgery also changes the way that gastrointestinal structures relate to each other. Specifically, the surgery prevents the distal stomach, duodenum, and part of the jejunum from direct contact with ingested material, and delays the mixing of ingested contents with hepatobiliary and pancreatic secretions.[5]

Lesson #1 of The Medical Student Notebook is a five-part series focused on gastrointestinal physiology. Each of the next five segments will discuss normal physiology and the effects of gastric bypass surgery with respect to the digestion and absorption of a particular nutrient or the activity of a key hormone. Some particularly interesting cases to study are the physiologically elegant mechanisms involved in absorbing vitamin B12 and iron. Additionally, the hormones leptin, ghrelin, and insulin are equally interesting from the perspective of hormonal regulation of the body’s catabolic and metabolic state. Analyzing these topics will provide a useful review of the underlying physiology of the gastrointestinal tract, and the effect of reorganizing that tract surgically.

Ultimately, the importance of understanding the impact of gastric bypass surgery is not limited to simply understanding the mechanisms of bariatric surgery. Greater understanding can help surgeons with the important task of managing patients’ nutritional status following procedures. Additionally, greater understanding of the hormonal mechanisms of bariatric surgery could suggest and enable future medical therapies for obesity or lead to modifications of surgical technique. Until then, bariatric surgery remains the only clinically proven treatment for refractory morbid obesity.

Part 1: Bariatric Surgery and Vitamin B12
This is the first of a five-part column focused on gastrointestinal physiology. Each column takes a particular aspect of gastrointestinal physiology, using it as an opportunity to reintroduce the core principles of gastrointestinal physiology and the implications of gastric bypass surgery for the body’s ability to digest and absorb key nutrients or hormonally regulate metabolism. The subject of this column will be the digestion and absorption of vitamin B12, a vital micronutrient.

B12, one of the water-soluble B vitamins, is an excellent springboard to discussing the implications of gastric bypass surgery because of the critical role vitamin B12 plays in the body, and also because the body utilizes one of the most unique and complex mechanisms to facilitate its digestion and absorption. The normal digestion and absorption of vitamin B12 highlights the pinnacle of complexity that can be required to facilitate digestion and absorption.[6] First, vitamin B12 must be ingested, mainly from animal products and fortified foods. In the stomach, gastric acid and pepsin isolate vitamin B12, which is able to combine with R-protein, a glycoprotein released in the saliva that is active in the stomach’s caustic environment. The stomach also secretes intrinsic factor, another glycoprotein. The vitamin B12 bound to R-protein travel along with secreted intrinsic factor to the duodenum where pancreatic enzymes release vitamin B12 from R-factor, at which time it binds with intrinsic factor in order to facilitate its absorption preferentially in the ileum.

Gastric bypass has many impacts on this elegant process of vitamin B12 absorption. Gastric bypass affects the body’s intake of foods, reducing B12 intake. The luminal surface of the stomach is also decreased, reducing the number of parietal and chief cells necessary to secrete gastric acid, pepsinogen, and intrinsic factor. What is equally interesting is that despite the disruption of the classic elegant multistep process, B12 deficiencies only affect 12 to 33 percent of gastric bypass patients.[7]

The surprising number of bariatric patients with adequate vitamin B12 intake is explained by numerous factors. Two protective mechanisms work to prevent the depletion.[8] The body also has large stores of vitamin B12, and colonic bacteria are capable of generating B12 directly in the digestive tract where it can be absorbed locally. A third critical protective mechanism is evident with careful attention to the physiologic consequences of gastric bypass. While vitamin B12 intake is decreased and there are fewer gastric secretions, vitamin B12 is still able to bind to R-protein in the stomach, and the anastomosis bringing pancreatic enzymes into contact with B12, R-protein, and intrinsic factor still occurs proximally to the ileum, which preserves its preferential site of absorption even following gastric bypass.

Gastrointestinal physiology shows that understanding basic principles can help physicians understand the underlying causes of nutritional deficiencies following gastric bypass, and can also help inform the approach to patient care. For example, by understanding that bariatric surgery, while impacting vitamin B12 absorption to a degree, does not eliminate any critical elements or disrupt the sequence of absorption. When vitamin B12 deficiency is encountered, oral repletion is a viable solution and is widely used in clinical practice.

References
1.    Wang YC, McPherson K, Marsh T, et al. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 2011;378(9793):815–825.
2.    Brolin RE. Bariatric surgery and long-term control of morbid obesity. JAMA. 2002 Dec 11;288(22):2793–2796.
3.    Desjeux JF. The molecular and genetic base of congenital transport defects. Gut. 2000;46(5):585–587.
4.    Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol. 2012;9(5):286–294.
5.    Xanthakos SA. Nutritional deficiencies in obesity and after bariatric surgery. Pediatr Clin North Am. 2009;56(5):1105–1121.
6.    Kozyraki R, Cases O. Vitamin B12 absorption: Mammalian physiology and acquired and inherited disorders. Biochimie. 2013;95(5):1002–1007.
7.    Brolin RE, Leung M. Survey of vitamin and mineral supplementation after gastric bypass and biliopancreatic diversion for morbid obesity. Obes Surg. 1999;9(2):150–154.
8.    Bal BS, Finelli FC, Shope TR, Koch TR. Nutritional deficiencies after bariatric surgery. Nat Rev Endocrinol. 2012;8(9):544–556.

FUNDING: No funding was provided for this article.
FINANCIAL DISCLOSURES: The authors report no conflicts of interest relevant to the content of this article.

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Category: Past Articles, The Medical Student Notebook

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