Water soluble vitamins deficiency Notes

NOTES NOTES WATER SOLUBLE VITAMINS DEFICIENCY GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Vitamin: micronutrient that participates in essential cellular function SIGNS & SYMPTOMS ▪ See individual disorders DIAGNOSIS CAUSES ▪ Insufficient water-soluble vitamin intake → ↑ demand, malabsorption, loss → insufficient for body’s metabolic needs COMPLICATIONS ▪ Chronic water-soluble vitamin deficiency → specific clinical disorders OTHER DIAGNOSTICS ▪ History, clinical presentation TREATMENT OTHER INTERVENTIONS ▪ ↑ dietary intake ▪ Synthetic formulation supplementation ▪ Address complications FOLATE (VITAMIN B9) DEFICIENCY osms.it/folate-(vitamin-b9)-deficiency PATHOLOGY & CAUSES ▪ Insufficient folate (pteroylglutamic acid) for body’s metabolic needs ▪ Body cannot synthesize, normally maintains low stores ▪ Folate must be obtained in diet; lack for several weeks → deficiency ▪ Folate deficiency → impaired DNA synthesis during erythropoiesis (cell cycle S-phase delay) → uncoordinated cytoplasm, nuclei maturation in erythroblasts (nuclear-cytoplasmic asynchrony) → ineffective hematopoiesis → ↑ erythroid apoptosis + abnormally large erythrocytes (macrocytosis) → defective cells with fragile membranes → ↓ red blood cell (RBC) lifespan → anemia Sources of folate ▪ Present naturally in plant (especially dark green leafy vegetables), animal products (especially liver) ▪ Folic acid available in dietary supplements, fortified foods (e.g. cereals) Recommended dietary allowances (RDAs) ▪ Folate RDAs listed as micrograms of dietary folate equivalents (DFEs), reflect OSMOSIS.ORG 301

▪ ▪ ▪ ▪ higher bioavailability in food vs. supplement Child 9–13: 300mcg DFE 14+: 400mcg DFE Pregnancy: 600mcg Lactation: 500mcg RISK FACTORS Insufficient diet ▪ Alcohol abuse ▫ Impairs folate absorption, metabolism; accelerates breakdown ▪ Chronic systemic disease; mental illness; advanced age ▪ Food insecurity ▪ Self-imposed dietary restrictions (e.g. vegan) ▪ ↓ vitamin C (cofactor for folate metabolism) Adequate diet but increased requirements ▪ Pregnancy, lactation, malignancy ▪ Disease state with ↑ cellular turnover (e.g. chronic hemolysis, exfoliative skin disease) Malabsorption ▪ E.g. celiac disease, inflammatory bowel disease, gastric surgery, achlorhydria Metabolic interference from medication ▪ E.g. methotrexate (folate antagonist), phenytoin, trimethoprim Hereditary forms ▪ Hereditary folate malabsorption (HFM) ▫ Loss-of-function mutation of PFCT gene encoding for proton-coupled folate transporter (rare, autosomal recessive disorder) ▪ Infantile cerebral folate deficiency ▫ Autoantibody against folate receptor in choroid plexus → prevents folate transport across blood-brain barrier COMPLICATIONS ▪ Megaloblastic anemia ▪ Insufficient folate during gestation → ↑ neural tube defect risk ▪ Developmental delay, neurological disorders (child) 302 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Megaloblastic anemia ▫ Hypoxemia, tissue hypoxia → fatigue, activity intolerance, pallor, ↑ heart rate ▪ ↑ hemolysis → jaundice ▪ Atrophic glossitis, angular stomatitis, anorexia, nausea, diarrhea ▪ Hereditary folate malabsorption ▫ Manifests at age 1–3 months ▫ Failure to thrive, neurologic deterioration, megaloblastic anemia ▪ Infantile cerebral folate deficiency ▫ Manifests at age 4–6 months ▫ Irritability, ↓ sensorineural hearing, seizure, developmental delay, sleep disturbance → visual disturbance/loss DIAGNOSIS LAB RESULTS ▪ ↓ RBC count; ↓ reticulocyte count; evidence of megaloblastic anemia (↑ mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH)) ▪ Macrocytosis, anisocytosis, poikilocytosis, hypersegmented neutrophils ▪ ↑ hemolysis markers ▫ ↓ indirect bilirubin, ↓ lactate dehydrogenase, ↓ haptoglobin ▪ ↓ serum folate ▪ Hypercellular bone marrow ▪ Infantile cerebral folate deficiency ▫ Cerebrospinal fluid (CSF) assay shows ↓ 5-methyltetrahydrofolate ▫ Serum, RBC folate normal TREATMENT OTHER INTERVENTIONS ▪ Address complications (e.g. neurologic manifestation) ▪ ↑ dietary folate intake ▪ Folic acid supplementation (synthetic formulation)

Chapter 53 Water Soluble Vitamins Deficiency NIACIN (VITAMIN B3) DEFICIENCY osms.it/niacin-(vitamin-b3)-deficiency PATHOLOGY & CAUSES ▪ Insufficient niacin (nicotinic acid, nicotinamide) for body’s metabolic needs ▫ Niacin obtained in diet ▫ Liver converts tryptophan to niacin (60g tryptophan = 1mg niacin) ▪ Active forms ▫ Nicotinamide adenine dinucleotide (NAD+), nicotinamide adenine dinucleotide phosphate (NADP+) ▪ Moderate/↑ doses of niacin supplement → ↓ total/low-density lipoprotein (LDL) cholesterol Sources of niacin ▪ Present in plant, animal products (e.g. dairy products, meat, grain (↓ corn), legumes, seeds) ▪ Dietary supplement; enriched grain, cereal, milk Metabolic defects ▪ E.g. carcinoid syndrome → impaired tryptophan metabolism Accelerated niacin depletion ▪ Prolonged isoniazid use → ↓ pyridoxal phosphate (active form of vitamin B6) → ↑ tryptophan synthesis Tryptophan-to-niacin conversion nhibited by medication ▪ E.g. phenobarbital, chloramphenicol, pyrazinamide COMPLICATIONS ▪ Pellagra RDAs ▪ Children 9–13: 12mg ▪ 19+ male: 16mg; 19+ female: 14mg ▪ Pregnancy: 18mg ▪ Lactation: 14mg RISK FACTORS Insufficient niacin/tryptophan intake ▪ Alcohol abuse ▪ Self-imposed dietary restrictions ▪ Chronic systemic disease; mental illness; advanced age ▪ Food insecurity ▪ Corn-based diet (unless corn treated with alkali, e.g. tortillas) Malabsorption ▪ E.g. bariatric surgery, malabsorptive disease states ▪ Hartnup disorder: defective tryptophan absorption Figure 53.1 A desqauamating rash on the skin of an individual who presented with diarrhea and confusion. The diagnosis was confirmed as pellagra. OSMOSIS.ORG 303

SIGNS & SYMPTOMS ▪ Dermatitis ▫ Photosensitive, pigmented ▪ Diarrhea ▫ Potentially also vomiting ▪ Dementia ▫ Potentially also anxiety, disorientation ▪ Death ▫ Untreated pellagra potentially fatal DIAGNOSIS LAB RESULTS ▪ ↓ N-methylnicotinamide (niacin metabolism product) TREATMENT OTHER INTERVENTIONS ▪ Niacin supplementation ▪ ↑ dietary niacin/tryptophan ▪ Address complications VITAMIN B12 DEFICIENCY osms.it/vitamin-b12-deficiency PATHOLOGY & CAUSES ▪ Insufficient B12 for body’s metabolic needs ▪ Active cobalamin (coenzyme) forms: methylcobalamin, 5-deoxyadenosylcobalamin ▪ Dietary cobalamin in food protein → gastric hydrochloric acid, protease-free cobalamin → cobalamin + intrinsic factor complex → distal ileum absorption ▪ Cobalamin essential for metabolic reactions involving hematopoiesis; protein, DNA, RNA, myelin synthesis; gastrointestinal tract mucosa maintenance ▫ Methylcobalamin: methionine synthase (folate-dependent enzyme) cofactor → methionine synthase catalyzes homocysteine remethylation to form methionine (essential amino acid for tissue growth/repair; hormone, protein, purine, pyrimidine synthesis) ▫ 5-deoxyadenosylcobalamin: L-methylmalonyl-coenzyme A conversion to succinyl CoA → enters citric acid cycle → lipid, protein energy production ▪ Impaired DNA synthesis during erythropoiesis (e.g. cell cycle S-phase delay) → uncoordinated cytoplasm, 304 OSMOSIS.ORG nuclei maturation in erythroblasts (nuclear-cytoplasmic asynchrony) → ineffective hematopoiesis → ↑ erythroid apoptosis, abnormally large erythrocytes (macrocytosis) → defective cells with fragile membranes → ↓ RBC lifespan → anemia Sources of cobalamin ▪ Animal products (meat, egg, dairy) ▪ Supplements, enriched food RDAs ▪ Child 9–13: 1.8mcg ▪ 14+: 2.4mcg RISK FACTORS Insufficient intrinsic factor ▪ Pernicious anemia ▫ Autoimmune condition destroys parietal cells → ↓ intrinsic factor production → cobalamin not absorbed ▪ Gastrectomy, bariatric surgery ▪ Gastric atrophy Malabsorption ▪ Achlorhydria (acid promotes gastric mucosa absorption) ▫ ↑ age → ↑ risk ▫ ↓ acid due to medication (e.g. antacid,

Chapter 53 Water Soluble Vitamins Deficiency H2 receptor blocker, proton pump inhibitor) ▫ Ileal resection, disease (e.g. celiac disease) Insufficient diet ▪ Alcohol abuse ▪ Chronic systemic disease, mental illness, advanced age ▪ Food insecurity ▪ Self-imposed dietary restrictions (e.g. vegan) Adequate diet but increased requirements ▪ Pregnancy, lactation, malignancies ▪ Disease states with ↑ cellular turnover (e.g. chronic hemolysis, exfoliative skin disease) Medication interfering with absorption ▪ E.g. Metformin, cycloserine, isoniazid, neomycin Fish tapeworm Diphyllobothrium latum infestation ▪ Competes for absorption in ileum Imerslund–Gräsbeck syndrome ( juvenile megaloblastic anemia) ▪ Autosomal recessive disorder ▪ Vitamin B12-intrinsic factor receptor defect cblD inborn error of cobalamin metabolism ▪ MMADHC gene mutation → MMADHC protein defect (cobalamin transporter) COMPLICATIONS ▪ Macrocytic anemia ▪ Neurodegenerative disorder ▪ ↑ hemolysis → jaundice ▪ ↓ gastrointestinal tract mucosa integrity → atrophic glossitis, angular stomatitis, anorexia, nausea, diarrhea ▪ Impaired myelin production → cognitive impairment, paresthesias, impaired proprioception, gait disturbance, slowed cognition DIAGNOSIS LAB RESULTS Blood study ▪ ↓ cobalamin ▪ CBC ▫ ↓ RBC count; ↓ reticulocyte count; megaloblastic anemia (↑ MCV, ↓ MCH) ▪ Blood smear analysis ▫ Macrocytosis, oval macrocytes; anisocytosis; poikilocytosis; hypersegmented neutrophils ▪ ↑ hemolysis markers ▫ Elevated indirect bilirubin, lactate dehydrogenase, ↓ haptoglobin Hypercellular bone marrow TREATMENT OTHER INTERVENTIONS ▪ ↑ dietary cobalamin ▪ Supplementation (cyanocobalamin) ▫ Pernicious anemia → parenteral cobalamin ▪ Address complications SIGNS & SYMPTOMS ▪ High body stores → 1–2 years insufficient intake → symptoms (adult/child) ▪ B12-deficient mothers → infant cobalamin deficiency sequelae at age 6–18 months ▪ Megaloblastic anemia ▫ Hypoxemia, tissue hypoxia → fatigue, activity intolerance, pallor, ↑ heart rate OSMOSIS.ORG 305

VITAMIN C DEFICIENCY osms.it/vitamin-c-deficiency PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Insufficient vitamin C for body’s metabolic needs ▪ Body cannot synthesize, must obtain in diet ▪ Active form: L-ascorbic acid ▪ ↓/no intake → symptoms within one month ▪ Mucocutaneous signs ▫ Spongy gums → loose teeth ▫ Capillary fragility → petechiae, ecchymoses, perifollicular hemorrhage, subperiosteal hemorrhage ▫ Hair structure changes → corkscrew hair ▪ Inability to maintain bone matrix ▫ Arthralgias, bone structure changes ▪ Anemia ▫ Fatigue, malaise ▪ Impaired wound healing RDA ▪ 9–13 years old: 45mg ▪ 14–18 years old: 75 mg (biologically-male); 65mg (biologically-female) ▪ 19+ years old: 90 mg (biologically-male); 75mg (biologically-female) ▪ Pregnancy: 85mg ▪ Lactation: 120mg ▪ Smokers: ↑ 35mg/day RISK FACTORS Insufficient diet ▪ Food insecurity ▪ Self-imposed dietary restrictions ▪ Chronic systemic disease, mental illness, advanced age ▪ Feeding infants evaporated/boiled cow’s milk ↑ oxidative stress ▪ Smoking, secondhand smoke COMPLICATIONS ▪ Scurvy, related sequelae (e.g. periodontal disease; bone, joint disorders) ▪ Impaired wound healing ▪ Weakened immune system ▪ Depression ▪ Microcytic anemia 306 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING MRI ▪ Sclerotic, lucent metaphyseal bands, soft tissue edema TREATMENT OTHER INTERVENTIONS ▪ ↑ dietary/supplementation vitamin C ▫ Present in many fruits, vegetables (especially citrus, tomatoes, broccoli, bell peppers, potatoes) ▫ Supplements, enriched grains ▪ Address complications

Chapter 53 Water Soluble Vitamins Deficiency Figure 53.2 An X-ray of the leg of a child with scurvy. There is a dense zone of provisional calcification at the epiphysis, known as a Frankel line, with underlying radiolucency known as a Trümmerfeld zone. OSMOSIS.ORG 307