STEPTRACKERBIOCHEMISTRY | NUTRITION | HIGH-YIELD REVIEW

Fat-Soluble Vitamins

A, D, E and K need bile and pancreatic lipase to be absorbed — so fat malabsorption steals all four at once, and excess can accumulate.

FOCUS ON

Deficiency of all four: cystic fibrosis, celiac, Crohn, cholestasis, orlistat, mineral oil. A: night blindness, Bitot spots; excess → IIH, teratogen. D: rickets/osteomalacia; excess → hypercalcemia (granulomas). E: hemolysis + dorsal column/spinocerebellar signs (mimics B12, but no megaloblasts); excess → bleeding with warfarin. K: ↑ PT bleeding; newborns get IM vitamin K.

VITAMIN

FUNCTION

DEFICIENCY

EXCESS · CLUE

Vitamin A

retinol

Visual pigment (rhodopsin), epithelial differentiation (retinoic acid receptors), immune function

Night blindness, xerophthalmia, Bitot spots, keratomalacia, dry scaly skin, squamous metaplasia, ↑ infections (measles severity)

Acute: nausea, vertigo · chronic: alopecia, dry skin, hepatotoxicity, idiopathic intracranial hypertension · teratogen (cleft palate, cardiac)

Vitamin A as drug

All-trans retinoic acid differentiates promyelocytes; isotretinoin shrinks sebaceous glands

—

ATRA for APL t(15;17) · isotretinoin: 2 forms of contraception (iPLEDGE)

Vitamin D

D₂ ergocalciferol · D₃ cholecalciferol

Skin (UVB) makes D₃ → liver 25-hydroxylation → kidney 1α-hydroxylation (PTH ↑) → calcitriol ↑ gut Ca²⁺ and PO₄³⁻ absorption, bone mineralization

Rickets (children: bowed legs, rachitic rosary, craniotabes) · osteomalacia (adults) · hypocalcemic tetany

Excess: hypercalcemia, kidney stones, confusion · granulomas (sarcoid, TB) make calcitriol

Vitamin D markers

25-OH D = best storage marker; 1,25-(OH)₂ D = active form

Deficiency: ↓ Ca, ↓ PO₄, ↑ PTH, ↑ ALP

Breastfed infants, dark skin, low sun, CKD (no 1α-hydroxylase)

Vitamin E

tocopherol

Antioxidant protecting membranes (RBCs, neurons) from lipid peroxidation

Hemolytic anemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar degeneration, ataxia, retinopathy

Neuro picture mimics B12, but no megaloblastic anemia or ↑ MMA · excess ↑ warfarin effect

Vitamin K

K₁ phylloquinone · K₂ from gut bacteria

Cofactor for γ-carboxylation of factors II, VII, IX, X, protein C, S

Bleeding with ↑ PT/INR (and ↑ PTT), normal bleeding time

Newborns: sterile gut, poor placental transfer → IM vitamin K at birth · long-term antibiotics

Warfarin interaction

Warfarin inhibits vitamin K epoxide reductase

—

Reverse with vitamin K (slow) ± prothrombin complex concentrate (fast)

Malabsorption pattern

Bile acids and lipase form micelles needed for absorption

All four deficient together; steatorrhea

CF, celiac, chronic pancreatitis, short bowel, cholestasis, orlistat

Abetalipoproteinemia

MTP defect → no chylomicrons/VLDL (no ApoB-48/100)

Fat malabsorption, acanthocytes, ataxia, retinitis pigmentosa (vitamin E and A loss)

Treat with high-dose vitamin E

Mechanism — activating vitamin D

Skin UVB / dietD₃ or D₂

→

Liver25-hydroxylase → 25-OH D

→

Kidney1α-hydroxylase (↑ PTH, ↓ PO₄)

→

Calcitriol↑ Gut Ca²⁺/PO₄³⁻, bone

Activated macrophages in granulomas have their own 1α-hydroxylase — PTH-independent hypercalcemia in sarcoidosis.

Which vitamin is missing?

CLUE

VITAMIN

WHY

Can't see at night

Rhodopsin

Bowed legs, ↑ ALP

Poor mineralization

Ataxia + hemolysis

Membrane oxidation

Newborn bleeding, ↑ PT

No carboxylated factors

How it's tested

COMMON CONFUSIONVitamin E deficiency and B12 deficiency both damage dorsal columns — E gives hemolysis without megaloblasts and normal methylmalonic acid.

THE TRAPHeadache and papilledema in a teen on acne treatment or eating lots of liver → vitamin A toxicity (pseudotumor cerebri).

YOUR APPROACHLook for a fat malabsorption setting → which of A, D, E, K fits the symptom → excess states for the supplement user.

If you see… think…

Night blindness, Bitot spots, child in low-income country → vitamin A deficiency

Papilledema in a teen on isotretinoin → vitamin A excess (IIH)

APL treated by inducing differentiation → all-trans retinoic acid

Breastfed dark-skinned infant with rachitic rosary → vitamin D deficiency

Sarcoidosis with high calcium → granuloma 1α-hydroxylase

Ataxia, ↓ vibration sense, hemolytic anemia in CF → vitamin E deficiency

Newborn bleeding day 2–7 with ↑ PT → vitamin K deficiency

Bleeding on warfarin after vitamin E megadoses → E potentiates warfarin

All four fat-soluble vitamins low + steatorrhea → fat malabsorption

Acanthocytes, ataxia, retinitis pigmentosa, no ApoB → abetalipoproteinemia