HMIM224 Block: Hematopoietic Vitamins

Study Notes

The course covers the role of vitamins as micronutrients, types of vitamins, biochemistry of water-soluble vitamins, their importance in red blood cell formation, biochemistry of fat-soluble vitamins, and the role of vitamin K in blood coagulation.

Water-soluble vitamins: Absorbed directly into the blood, circulate freely, excreted in urine, less likely to be toxic, include thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folic acid (B9), and cobalamin (B12), and ascorbic acid (C). Required every 2-3 days.
Fat-soluble vitamins: Require carriers (chylomicrons) to circulate in lymph; stored in cells with fat, more likely to be toxic, include vitamin A, vitamin D, vitamin E, and vitamin K. Required weekly.

Pyridoxine (B6): A coenzyme for ALA synthase in heme synthesis (detailed in GIT block)
Folic acid (B9): Essential for purines and thymidine nucleotides needed for DNA synthesis; crucial for cell division and maturation of red blood cells. Obtained through diet, though some microorganisms synthesize it. Active form: Tetrahydrofolate (THF).
Cobalamin (B12): Required for converting homocysteine to methionine; vital for DNA synthesis and nerve myelination. Found in animal products. Active forms are adenosylcobalamin and methylcobalamin.
Ascorbic acid (vitamin C): A reducing agent, aiding iron absorption, acting as an antioxidant, and being critical for collagen synthesis.

Causes: Increased demand (pregnancy/lactation), poor absorption, anti-folate drugs, or a folate-free diet.
Effect: Megaloblastic anemia (diminished purine synthesis in DNA).
Note: Crucial to diagnose the cause before initiating therapy as vitamin B12 deficiency can have similar symptoms. Folic acid supplements routinely given to pregnant women.

Causes: Dietary deficiency (vegetarians), poor absorption (autoimmune destruction of gastric parietal cells - pernicious anemia, gastrectomy, or ileal resection), or drugs.
Effect: Neurological manifestations (neuropathy, demyelination) and megaloblastic anemia (folate trap, impacting purine synthesis).

Types: Vitamin K1 (phylloquinone) – found in plants; Vitamin K2 (menaquinones) – synthesized by intestinal flora and found in animals.
Absorption: Requires bile for absorption.
Role: Essential for normal blood coagulation, participating in the synthesis of coagulation factors (prothrombin, VII, IX, and X) and anticoagulant proteins. Activating clotting factors by binding to calcium ions and undergoing y-carboxylation of glutamic acid residues.
Deficiency Causes: Dietary deficiency (rare), destruction of normal bacterial flora (antibiotics), drugs (cephalosporins), malabsorption of lipids, and deficiency in newborns.
Clinical Manifestations: Hemorrhagic disease of the newborn, internal bleeding, tendency to bruise.

Symptoms: Hemorrhagic disease of the newborn, bruising tendency, ecchymosis, and internal bleeding.
Lab Investigations: Hypoprothrombinemia with increased blood coagulation time and prolonged prothrombin time.

Anticoagulants: Warfarin and dicoumarol are vitamin K analogs that inhibit clotting factor production and vitamin K epoxide reductase (VKOR) competitively, thus affecting the function of the vitamin K.