GI Nutrition: GI Nutrition: Minerals and Trace Elements

0:00Welcome to Board Pearls. This is episode four of four, the last episode of the GI Nutrition chapter, in the Special Populations and Acute or Supportive Care module. This episode is the minerals and trace elements, each matched to the exposure or disease that tips it into deficiency or excess. The first patient is a man with an unsteady gait who uses a lot of denture cream, and his case shows how too much zinc causes copper deficiency, why it looks like B12 deficiency, and why zinc replacement has to be watched. The woman on a long-term proton pump inhibitor from episode three shows how that drug lowers magnesium. The woman on home parenteral nutrition from episode two shows why manganese collects in the brain once the liver stops clearing it, and which elements an unsupplemented bag leaves out. A man who snacks on Brazil nuts shows what too much selenium does to hair and nails. And patients after gastric bypass and with cholestasis show how iron is replaced and why calcium is best taken as food.

1:00Here's the patient. A sixty-six-year-old man has an unsteady, wide-based gait and numbness in his legs, worsening over a year. His hemoglobin and neutrophil count are low, and his red cells are slightly large. His neurologist suspected subacute combined degeneration from B12 deficiency, but his B12, his methylmalonic acid, MMA, and his folate are all normal. He wears full dentures that fit poorly and uses several tubes of denture cream a week.

1:27He has copper deficiency myeloneuropathy, caused by zinc excess from his denture cream. The findings that point to it are a spinal cord and nerve picture that looks like B12 deficiency, anemia with neutropenia, a normal B12, and a heavy zinc exposure. Each mineral and trace element produces its own clinical picture, because each has a specific biochemical job and a typical exposure or disease that causes its deficiency or excess, often through a single mechanism. In him that mechanism is zinc trapping copper. In others it's cholestasis blocking manganese excretion or Brazil nuts concentrating selenium. So the exposure is asked about first, because it usually explains the whole picture.

2:10His gait looks like B12 deficiency because copper deficiency injures the same spinal cord and nerves. Copper deficiency produces a myeloneuropathy with sensory ataxia and gait disturbance, plus anemia and neutropenia. The anemia is most often normocytic or macrocytic, like his, and occasionally microcytic. Copper is needed for cytochrome c oxidase in energy metabolism, and its failure in neurons causes the neurologic injury. It's needed for lysyl oxidase in connective tissue and nerve. And it's needed for ceruloplasmin to release iron from cells to transferrin, so without copper, iron stays trapped in cells and red cell production can become iron-restricted, which is why a microcytic picture appears at all. The discriminator from B12 deficiency is a normal B12, and his normal B12 and MMA send his workup to serum copper and ceruloplasmin. Both are low in deficiency, and both are low in him. The woman in episode three had a high MMA, so her cord disease was B12; his isn't.

3:16His copper was lost to the zinc in his denture cream. Chronic zinc excess, from older denture creams that contained substantial zinc, excessive supplements, or industrial exposure, induces metallothionein in the cells lining the small bowel. Metallothionein binds copper preferentially and holds it in those cells, which are shed before the copper reaches portal blood. Patients rarely volunteer denture cream or zinc pills, so they're asked about by name. The other settings for copper deficiency are gastric bypass, which reduces copper absorption in the duodenum, and, rarely, prolonged parenteral nutrition without copper. His treatment is oral copper, two milligrams daily, with removal of the zinc source, so he changes to a zinc-free adhesive and starts copper.

4:03Taking away his zinc source is safe, but driving zinc too low causes its own disease, which is why zinc replacement is always watched. Zinc deficiency causes periorificial dermatitis, called acrodermatitis enteropathica in its inherited form, plus alopecia, diarrhea, poor wound healing, dysgeusia, and immune dysfunction. In cirrhosis, hepatic encephalopathy that won't respond to treatment can reflect zinc deficiency, because zinc is a cofactor for ornithine transcarbamylase in the urea cycle. The settings are short bowel syndrome, severe Crohn disease, alcohol use disorder, celiac disease, and prolonged unsupplemented parenteral nutrition. Picture a man with short bowel syndrome who develops a red, scaly rash around his mouth, a wound that won't heal, and altered taste. He gets a zinc level, and if it's low, oral zinc sulfate, two hundred twenty milligrams daily, which is fifty milligrams of elemental zinc. His replacement is monitored, because excess zinc is exactly what caused copper deficiency in the man with the dentures.

5:07A drug can strip a mineral as surely as zinc strips copper, and the woman from episode three shows it. She's the seventy-three-year-old who took a proton pump inhibitor, PPI, for many years and developed B12 deficiency. Suppose she's later admitted with tetany and a seizure, and her magnesium is very low, with normal kidney function, no diuretic, and no alcohol use. She has PPI-induced hypomagnesemia. The Food and Drug Administration issued a warning in twenty eleven after case reports and cohort studies linked long-term PPI use to symptomatic hypomagnesemia. The mechanism is impaired function of the TRPM6 magnesium channel in the distal convoluted tubule under chronic acid suppression, although the exact link between gastric pH and that channel isn't fully understood. The signature is tetany, seizure, or arrhythmia from low magnesium in a long-term PPI user with normal kidneys and no diuretic or alcohol cause, which describes her.

6:06Her treatment follows from the cause, so the drug goes first. Stopping a PPI normalizes magnesium within about a week, and restarting it brings the low magnesium back within about two. Where it's feasible, her PPI is stopped and an H2 blocker substituted. Her magnesium is replaced intravenously, as magnesium sulfate, because she's symptomatic and in hospital; an outpatient would take oral magnesium oxide or magnesium chloride. And her team asks whether she needs acid suppression at all. Her one drug would then account for both of her deficiencies, B12 and magnesium.

6:42Parenteral nutrition causes the opposite problem, an element building up instead of running short, and the woman from episode two shows why. She's the thirty-nine-year-old with Crohn disease and enterocutaneous fistulas on home parenteral nutrition. Manganese is needed for manganese superoxide dismutase and glutamine synthetase, but dietary deficiency essentially doesn't occur, because the requirement is small and the supply ample. The clinical problem is toxicity from long-term parenteral nutrition. Manganese is normally excreted in bile, so when cholestasis develops, from intestinal failure-associated liver disease or other causes, disposal fails. And intravenous delivery skips the gut barrier that normally limits how much is absorbed.

7:25If she develops cholestasis and then a tremor and stiffness, her manganese is the likely cause. It accumulates in the basal ganglia, particularly the globus pallidus, with T1 hyperintensity on magnetic resonance imaging, MRI, and parkinsonian signs, rigidity, bradykinesia, and postural instability, that may not respond to levodopa. So she has an MRI, and a bright globus pallidus on T1 confirms it. Manganese is removed from her parenteral nutrition formula once cholestasis develops or once the T1 change is seen, whichever comes first.

8:01Her bag can also be short of what it should contain, and two deficiencies show up mainly on long-term unsupplemented parenteral nutrition. Selenium deficiency causes cardiomyopathy, known as Keshan disease in selenium-deficient regions of China, along with more oxidative damage, because selenium is a cofactor for glutathione peroxidase, and thyroid dysfunction, because the deiodinase enzymes are selenoproteins. It's rare in industrialized populations, so a new cardiomyopathy in her would raise selenium. Chromium deficiency on chromium-free parenteral nutrition causes glucose intolerance, because chromium is a cofactor in insulin signaling, and repletion restores normal glucose. Unexplained rising sugars on her parenteral nutrition would raise chromium.

8:45Selenium can also be too high, and the cause is usually a snack. A forty-eight-year-old man notices his hair thinning, his nails becoming brittle with long streaks and lifting from the nail bed, and a garlic smell on his breath, with tingling in his feet and some stomach upset. He eats a handful of Brazil nuts every day. He has selenosis. Brazil nuts concentrate selenium so heavily that a single nut can contain one hundred micrograms or more, several times the daily requirement, and the classic setting is more than three nuts a day, chronically. The garlic breath comes from exhaled dimethyl selenide. His treatment is cutting back his selenium intake, and the diagnosis comes from asking about his snacks.

9:26Iron deficiency in a nutrition setting connects back to gastric bypass, which lowers copper absorption and also bypasses the duodenum, the main site of iron absorption. A forty-one-year-old woman after gastric bypass has iron deficiency anemia. In this context, iron deficiency comes from chronic gastrointestinal blood loss, from malabsorption, classically celiac disease with proximal villous atrophy, covered in chapter ten, from increased demand in pregnancy and growth, or from bariatric anatomy like hers. She starts oral ferrous sulfate. If she can't tolerate it or doesn't absorb it, she gets intravenous iron instead. A response shows as rising reticulocytes within seven to ten days, with hemoglobin recovering over weeks.

10:10Calcium matters most in patients whose bones are already threatened, which brings back the first woman from episode three, with primary biliary cholangitis, vitamin D deficiency, and osteoporosis. Calcium intake remains essential for bone health in postmenopausal women, in inflammatory bowel disease treated with chronic steroids, after bariatric surgery, in chronic cholestasis with vitamin D deficiency, and in cirrhosis with sarcopenic bone disease. The question is how she gets it. Meta-analyses of calcium supplement trials suggested a possible increase in myocardial infarction, especially without vitamin D, and later analyses moderated that signal. The current consensus prefers dietary calcium, because it doesn't produce the plasma calcium peaks that may drive vascular calcification. So she takes her calcium with her vitamin D, from her diet where she can.

11:01Here are the traps the boards set in these patients. A myeloneuropathy that looks like subacute combined degeneration but comes with a normal B12 points to copper deficiency. Denture cream and zinc supplements cause copper deficiency, and patients don't mention them unless asked. Zinc replacement is monitored, because too much zinc causes copper deficiency. Zinc deficiency can be the reason hepatic encephalopathy won't respond in cirrhosis. A seizure, tetany, or arrhythmia in a long-term PPI user with low magnesium is PPI-induced hypomagnesemia, and the PPI is stopped. Manganese is removed from parenteral nutrition once cholestasis develops. A new cardiomyopathy on long-term parenteral nutrition raises selenium deficiency. Hair loss, streaked nails, and garlic breath point to Brazil nuts. And dietary calcium is preferred over calcium pills.

11:56So, start to finish. Match each element to its clue, and ask about the exposure first. Zinc excess from denture cream or supplements traps copper in the bowel lining, causing a copper deficiency that mimics B12 myeloneuropathy, with anemia and neutropenia but a normal B12; check copper and ceruloplasmin, give copper two milligrams daily, and remove the zinc. Zinc deficiency causes periorificial dermatitis, poor healing, and taste loss, can worsen encephalopathy in cirrhosis, and is replaced with zinc sulfate under monitoring. Long-term PPI use can cause symptomatic hypomagnesemia that resolves within about a week of stopping the drug.

12:40On parenteral nutrition, manganese builds up in the globus pallidus once cholestasis develops and comes out of the bag. An unsupplemented bag can cause selenium deficiency with cardiomyopathy, and chromium deficiency with glucose intolerance. Brazil nut excess causes selenosis, with hair and nail loss and garlic breath. Iron is replaced by mouth or, when that fails, by vein, with reticulocytes rising in seven to ten days. And dietary calcium is preferred over supplements.

13:08That completes chapter thirty-two. Chapter thirty-three is GI infections.

13:15For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode four of four of chapter thirty-two, and I'll see you in the next one.