Clinical Nutrition & Micronutrient Deficiencies

Assessing nutritional status

A clinical diagnosis. Malnutrition is recognized at the bedside, not by a single laboratory value. Two or more of the following support it: inadequate energy intake, unintentional weight loss, loss of muscle mass (temporal hollowing, interosseous and quadriceps wasting), loss of subcutaneous fat, fluid accumulation that can hide weight loss, and reduced grip strength. A BMI below 18.5 defines underweight, but normal-weight and obese patients can also be malnourished.

Why not albumin. Albumin (half-life about 20 days) and prealbumin (about 2 days) are negative acute-phase reactants: inflammation suppresses their synthesis, and they also fall with liver disease, nephrotic or gastrointestinal protein loss, and hemodilution. Low values signal illness severity and prognosis, not recent intake or the response to feeding.

Feeding route and refeeding syndrome

Enteral first. If the gut works, use it. Enteral nutrition maintains the intestinal mucosa and gut-associated immunity, limits bacterial translocation, causes fewer infections, and costs far less than parenteral feeding. Nasogastric tubes suit short-term feeding, post-pyloric tubes help with aspiration risk or gastroparesis, and a gastrostomy is placed when feeding will be needed beyond about 4 weeks. Enteral problems include aspiration, diarrhea, tube dislodgement, and sinusitis with nasal tubes. In advanced dementia, tube feeding neither prolongs survival nor prevents aspiration, so careful hand feeding is preferred.

Parenteral nutrition. TPN is reserved for a gut that cannot be used: short bowel syndrome, obstruction, prolonged ileus, high-output fistula, or severe malabsorption. Central venous access brings catheter-related bloodstream infection (including Candida) and thrombosis. Metabolic risks include hyperglycemia, refeeding shifts, hypertriglyceridemia from lipid emulsions, and trace element deficiencies if additives are omitted. Prolonged TPN also causes hepatic steatosis, cholestasis, and gallbladder sludge because there is no enteral stimulus for gallbladder contraction.

Refeeding syndrome. During starvation, intracellular phosphate, potassium, and magnesium are depleted even when serum levels look normal. Carbohydrate triggers insulin release, which drives these ions into cells and consumes thiamine. Hypophosphatemia is the hallmark, usually within the first few days: loss of ATP and red-cell 2,3-BPG produces respiratory muscle failure, heart failure, arrhythmias, rhabdomyolysis, hemolysis, confusion, and seizures, while sodium and water retention cause edema and thiamine depletion can precipitate Wernicke encephalopathy. Highest-risk patients have anorexia nervosa, chronic alcohol use, BMI below 16, little intake for more than 10 days, weight loss above 15% over 3–6 months, or low electrolytes before feeding.

Water-soluble vitamin deficiencies

Thiamine (B1). Thiamine pyrophosphate is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, transketolase, and branched-chain ketoacid dehydrogenase. Risk settings are alcohol use disorder, hyperemesis gravidarum, vomiting after bariatric surgery, and refeeding. Wernicke encephalopathy — confusion, ophthalmoplegia or nystagmus, and ataxia — is often incomplete, so treat on suspicion with high-dose IV thiamine before any glucose, which would consume the remaining thiamine. Untreated, it can progress to Korsakoff syndrome: permanent anterograde amnesia with confabulation from damage to the mammillary bodies and medial thalamus. Wet beriberi is high-output heart failure with vasodilation, tachycardia, and edema; dry beriberi is a symmetric distal sensorimotor polyneuropathy.

Vitamin B12. B12 is required by methionine synthase and methylmalonyl-CoA mutase. Deficiency causes macrocytic anemia with hypersegmented neutrophils and subacute combined degeneration — dorsal column loss of vibration and position sense with a positive Romberg sign, plus corticospinal spasticity and Babinski signs — which can occur without anemia. Methylmalonic acid and homocysteine both rise; folate deficiency raises homocysteine only. Causes include pernicious anemia (anti–intrinsic factor and parietal cell antibodies), strict vegan diets, gastrectomy and gastric bypass, metformin, long-term PPIs or H2 blockers, terminal ileal disease or resection, fish tapeworm, and nitrous oxide. Treat with IM cyanocobalamin or high-dose oral B12; folate alone can fix the anemia while the neuropathy advances.

Niacin (B3). Niacin forms NAD and NADP and can be synthesized from tryptophan in a B6-dependent pathway. Pellagra brings photosensitive dermatitis (including a Casal necklace), diarrhea, dementia, and, untreated, death. Beyond alcohol use and corn-based diets, suspect carcinoid syndrome (tryptophan diverted to serotonin), isoniazid (B6 depletion; prevented by coadministered pyridoxine), and Hartnup disease, an autosomal recessive defect in a neutral amino acid transporter that limits tryptophan absorption.

Vitamin C. Ascorbate is the cofactor for prolyl and lysyl hydroxylases that stabilize collagen, and it enhances nonheme iron absorption. Scurvy affects older adults on tea-and-toast diets, people with alcohol use disorder, and those with very restrictive diets: perifollicular hemorrhages, corkscrew hairs, swollen bleeding gums, easy bruising, hemarthrosis, poor wound healing, and anemia.

Fat-soluble vitamins and trace elements

Vitamin A. Retinal regenerates rhodopsin, so night blindness is the earliest symptom, followed by xerophthalmia, Bitot spots (foamy conjunctival keratin patches), keratomalacia, follicular hyperkeratosis, and impaired immunity. Fat malabsorption — cystic fibrosis, cholestasis, pancreatic insufficiency, malabsorptive bariatric surgery — and poor diets are the usual causes. In children with measles, vitamin A supplementation lowers complications and mortality.

Vitamin K. Vitamin K enables γ-carboxylation of factors II, VII, IX, and X and proteins C and S. Deficiency follows fat malabsorption, broad-spectrum antibiotics, prolonged NPO status or TPN without supplementation, and missed newborn prophylaxis. The PT/INR prolongs first because factor VII has the shortest half-life; bleeding and the PT correct with vitamin K.

Zinc. Deficiency produces periorificial and acral dermatitis, alopecia, diarrhea, dysgeusia, poor wound healing, hypogonadism, and infections. Acquired causes are malabsorption, chronic diarrhea, alcohol use, bariatric surgery, and TPN without trace elements; acrodermatitis enteropathica is the autosomal recessive infantile form caused by defects in the ZIP4 zinc transporter.

Copper. Copper deficiency causes a myeloneuropathy indistinguishable from B12-related subacute combined degeneration — sensory ataxia and spastic gait — plus anemia and neutropenia that can mimic myelodysplasia. It follows gastric bypass or other upper GI surgery, malabsorption, and excess zinc, which induces enterocyte metallothionein that binds copper. Serum copper and ceruloplasmin are low; stopping zinc and replacing copper restores blood counts, but neurologic deficits may persist.

Nutrition after bariatric surgery

Why deficiencies occur. Roux-en-Y gastric bypass diverts food past the duodenum and proximal jejunum, the main sites of iron and calcium absorption, and reduces gastric acid and intrinsic factor. Sleeve gastrectomy is less malabsorptive, whereas biliopancreatic diversion with duodenal switch adds losses of fat-soluble vitamins, zinc, and copper.

Monitoring. Correct deficiencies before surgery, then check CBC, iron studies and ferritin, B12, folate, 25-hydroxyvitamin D, calcium, and PTH every 3–6 months in the first year and yearly for life, adding vitamin A, zinc, and copper after malabsorptive procedures. Missed deficiencies cause anemia, secondary hyperparathyroidism with bone loss, and neuropathy.

Persistent vomiting in the weeks after bariatric surgery is a thiamine emergency: give IV thiamine before any dextrose.