Fat soluble vitamin deficiency Notes

NOTES NOTES FAT SOLUBLE VITAMINS DEFICIENCY GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Insufficient plasma concentrations of fat soluble vitamins required for normal metabolic processes RISK FACTORS ▪ Reduced intake, impaired absorption, increased elimination DIAGNOSIS ▪ See individual disorders TREATMENT OTHER INTERVENTIONS ▪ Increased dietary intake; supplementation SIGNS & SYMPTOMS ▪ See individual disorders VITAMIN D DEFICIENCY osms.it/vit-d-deficiency PATHOLOGY & CAUSES ▪ Body’s metabolic needs not met as there is insufficient 25-hydroxyvitamin D ▪ Liver, kidneys hydroxylate physiologically inert vitamin D ▫ Precursor molecule (7-dehydrocholesterol) exposed to ultraviolet light/dietary vitamin D → D3/D2 released into blood → first hydroxylation in liver → second hydroxylation in kidneys → metabolically active calcitriol (1,25-dihydroxyvitamin D) ▪ Insufficient vitamin D → ↓ intestinal absorption of calcium → ↓ serum calcium → ↑ serum PTH → ↑ intestinal calcium absorption + ↑ osteoclastic activity, calcium resorption from bones + ↑ renal conservation of calcium → normalization of serum calcium CAUSES ▪ Insufficient dietary, supplementary intake ▪ Increased need, but insufficient intake ▫ Pregnancy, lactation ▪ Obesity, vitamin D sequestration in adipose tissue ▪ Impaired absorption ▫ Small bowel disease; bariatric surgery; gastrectomy; pathology of hepatobiliary tree, pancreas; abetalipoproteinemia ▪ Decreased synthesis in skin ▫ Insufficient sun exposure; dark skin OSMOSIS.ORG 263

(large amounts of melanin in epidermal layer); excessive sunscreen ▪ Impaired liver, kidney hydroxylation ▫ Cirrhosis, renal failure ▪ Altered vitamin D metabolism from drugs ▫ Phenobarbital, phenytoin, rifampin, isoniazid, carbamazepine, ketoconazole Genetic mutations ▪ 1-alpha-hydroxylase deficiency: mutations in CYP27B1; previously called vitamin D-dependent rickets type 1A ▪ 25-hydroxylase deficiency: mutations in CYP2R1; previously called vitamin D-dependent rickets type 1B ▪ Hereditary resistance to vitamin D: mutations in VDR (vitamin D receptor gene); previously called vitamin D-dependent rickets type 2 RISK FACTORS ▪ Risk increases with age ▪ Gastrointestinal tract, liver, kidney conditions ▪ Medications that interfere with vitamin D metabolism ▪ Decreased ultraviolet light exposure ▫ Cold climate/high latitudes, institutionalization/incarceration Perinatal factors (↓ neonatal vitamin D stores) ▪ Exclusively breastfed infants ▫ Maternal vitamin D status dictates amount vitamin D in milk ▪ Premature birth ▫ Low stores of vitamin D ▪ Low maternal vitamin D during gestation COMPLICATIONS ▪ Related to accompanying hypocalcemia ▫ Osteoporosis ▫ Increased risk of fractures ▫ Osteomalacia ▫ Ricketts (children) ▫ Secondary hyperparathyroidism 264 OSMOSIS.ORG SIGNS & SYMPTOMS SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ Mild deficiency may be asymptomatic Decreased bone density, osteoporosis Fractures Dental enamel hypoplasia Severe deficiency ▫ Hypocalcemia-related osteomalacia symptoms ▫ Bone tenderness/pain ▫ Muscle weakness, cramping, numbness/ tingling, positive Trousseau sign, Chvostek’s sign ▫ Bone malformations: difficulty ambulating, waddling gait DIAGNOSIS DIAGNOSTIC IMAGING X-ray ▪ High-stress areas ▫ Fractures; vertebral compression fractures ▪ Radiolucent bands (indicate pseudofractures) ▪ Codfish vertebrae ▫ Biconcave vertebral discs ▪ Children ▫ Epiphyseal plate widening; osteopenic/ malformed long bone shafts, pathological fractures Dual-energy X-ray absorptiometry (DEXA) ▪ Decreased bone density LAB RESULTS ▪ Decreased serum 25-hydroxyvitamin D (calcidiol) level ▪ Elevated alkaline phosphatase (bone turnover marker) ▪ Decreased serum calcium ▪ Increased parathyroid hormone (PTH)

Chapter 44 Fat Soluble Vitamin Deficiency TREATMENT OTHER INTERVENTIONS ▪ Vitamin D3 supplementation ▫ Dietary: fish, egg yolk, fortified foods ▫ Supplementation ▫ Ultraviolet light/natural sunlight exposure ▪ Increase calcium intake VITAMIN K DEFICIENCY osms.it/vit-k-deficiency PATHOLOGY & CAUSES ▪ Body’s metabolic needs not met; insufficient vitamin K ▫ Coagulation function ▫ Bone biology ▫ Vascular biology ▪ Dietary vitamin K1 (phylloquinone) → bile salts make fat soluble vitamin soluble → incorporated into gastrointestinal tract’s micelles → absorbed by small intestine → integrated into chylomicrons → transported to portal circulation → liver uses to synthesize coagulation factors, other essential proteins TYPES Infancy: vitamin K-deficiency bleeding (VKDB) ▪ Early-onset VKDB: occurs within first 24 hours of life; caused by immature liver function, low stores of vitamin K at birth, sterile gut, exclusive breastfeeding (breastmilk low in vitamin K), medications present in maternal circulation interfering with vitamin K (anticonvulsants, warfarin) ▪ Classic VKDB: occurs between 1–4 weeks; prevented by vitamin K1 prophylaxis at birth ▪ Late-onset VKDB: occurs between 3 weeks–8 months; associated with lack of vitamin K1 prophylaxis at birth, exclusive breastfeeding (breastmilk low in vitamin K) ▫ Diseases of small intestines, liver, gallbladder, pancreas RISK FACTORS Infants ▪ No vitamin K1 prophylaxis at birth ▪ Immature liver uses vitamin K inefficiently ▪ Low vitamin K stores ▪ Sterile gut ▪ Maternal ingestion of coumarin-like anticoagulants/some anticonvulsants/ antibiotics during gestation ▪ Antibiotic administration (destroys developing gut flora) Adults ▪ Prolonged diarrhea ▪ Use of broad-spectrum antibiotics, low intake of vitamin K ▪ TPN administration without added vitamin K COMPLICATIONS ▪ Most common ▫ Bleeding, ranging from mild (mucocutaneous) to severe (intracranial hemorrhage most common in late onset VKDB) ▪ Impaired bone mineralization ▪ Vascular calcium deposits Later childhood, adulthood ▪ Fat absorption and vitamin K metabolism disorders OSMOSIS.ORG 265

SIGNS & SYMPTOMS ▪ Low bone density signs Impaired coagulation ▪ Mucocutaneous bleeding: gingival, nasal, easy bruising ▪ Gastrointestinal bleeding: melena ▪ Genitourinary bleeding: hematuria ▪ Neonatal bleeding: umbilical stump/ circumcision site ▪ Intracranial hemorrhage: vomiting, seizures DIAGNOSIS DIAGNOSTIC IMAGING DEXA ▪ Low bone mineralization 266 OSMOSIS.ORG LAB RESULTS ▪ Coagulation studies ▪ Prolonged prothrombin time (PT), partial thromboplastin time (PTT), International Normalized Ratio (INR) ▪ Elevated serum undercarboxylated proteins (proteins induced by vitamin K absence) TREATMENT OTHER INTERVENTIONS ▪ Administer Vitamin K ▫ Subcutaneous phytonadione ▪ ↑ dietary vitamin K ▫ Liver, green leafy vegetables (broccoli, spinach, kale)