Introduction to Hematopoietic Vitamins HMIM224

Introduction to Hematopoietic and Antihemorrhagic Vitamins

• HMIM224 Block focuses on vitamins crucial for blood formation (hematopoietic) and preventing bleeding (antihemorrhagic)
• Objectives of the lectures include:
  • Introduction to vitamins as micronutrients
  • Categorization of vitamins (water-soluble and fat-soluble)
  • Biochemistry of water-soluble vitamins and their role in red blood cell formation
  • Biochemistry of fat-soluble vitamins
  • Role of vitamin K in blood coagulation

Types of Vitamins

• Vitamins are categorized as water-soluble or fat-soluble based on their solubility properties
• Key water-soluble vitamins: Thiamine (B1), Riboflavin (B2), Niacin (B3), Pantothenic Acid (B5), Pyridoxine (B6), Biotin (B7), Folic Acid (B9), Cobalamin (B12), and Ascorbic Acid (C)
• Key fat-soluble vitamins: Retinol (vitamin A), Cholecalciferol (vitamin D), Tocopherol (vitamin E), and Phylloquinone (vitamin K)

Water-Soluble Vitamins

• Absorption: Directly absorbed into the bloodstream
• Transport: Circulate freely in the bloodstream
• Storage: Stored primarily in the urine, less stored in the body
• Excretion: Primarily through excretion in the urine
• Toxicity: Less likely to cause toxicity compared to fat-soluble vitamins
• Requirements: Needed every 2-3 days

Fat-Soluble Vitamins

• Absorption: Require carriers (like chylomicrons) to be absorbed into the lymph, then blood
• Transport: Transported in the blood with proteins
• Storage: Stored in body tissues with fats and cells
• Excretion: Harder to excrete through urine, stored with fats in cells
• Toxicity: More prone to toxicity due to storage in body tissues
• Requirements: Needed less frequently, often weekly

Water-Soluble Hematopoietic Vitamins

• Pyridoxine (B6): Coenzyme for ALA synthase (heme synthesis); detailed in GIT block
• Folic Acid (B9): Essential for DNA synthesis, cell division, and red blood cell maturation
• Cobalamin (B12): Crucial for DNA synthesis and nerve myelination. Also converts homocysteine to methionine.
• Ascorbic Acid (vitamin C): Helps in iron absorption and antioxidant

Folic Acid: Detail

• Chemistry: Its structure is shown in the infographic

• Sources: Found in vegetables, liver, and meat; susceptible to cooking degradation

• Synthesis: Not synthesized by humans, but by microorganisms

• Active Form: Tetrahydrofolate (THF): (activation occurs in human cells)

• Function: Essential for purines and thymidine nucleotides for DNA synthesis, important for cell maturation (especially erythroid progenitors)

• Deficiency Causes: nutritional deficiencies, GIT disease, medication like methotrexate

• Deficiency Effect: Megaloblastic anemia.

Vitamin B12: Detail

• Sources: Animal products (liver, meat, chicken), daily requirements of 5ug, stored in large numbers (5mg) in the liver
• Coenzyme Forms: Adenosylcobalamin and Methylcobalamin (active forms)
• Absorption: Requires intrinsic factor produced by the stomach for absorption in the small intestine (lower ileum)
• Importance: Vital for DNA synthesis, nerve myelination

Vitamin B12 Deficiency Causes

• Dietary deficiency (vegetarians):
• Malabsorption (problems with intrinsic factor production, gastric bypass, intestinal issues)

Vitamin B12 Deficiency: Clinical Manifestations

• Neurological symptoms (neuropathy, demyelination)
• Megaloblastic Anemia (folate trap)

Ascorbic Acid (Vitamin C): Detail

• Chemistry: Its structure is displayed in the materials
• Sources: Found in various fruits and vegetables, dietary sources are provided in the notes
• Function: Reducing agent, aids iron absorption, antioxidant, coenzyme for hydroxylases in collagen synthesis, critical for wound healing
• Deficiency: Scurvy (fatigue, sores, loose teeth, easy bruising)

Vitamin K: Detail

• Types: Vitamin K1 (phylloquinone—plant sources) and Vitamin K2 (menaquinone—synthesized by intestinal bacteria/animals)
• Absorption: Bile (from the liver) essential for fat-soluble vitamin absorption
• Role in Hematopoiesis: Necessary for final stage in the synthesis of coagulation factors (VII, IX, X, prothrombin and anticoagulation, proteins). Activates factors via carboxylation of glutamate residues which permits calcium and phospholipid binding.
• Deficiency: Hemorrhagic (bleeding) disease of the newborn, a possible source being lack of gut colonization in newborns.

Vitamin K Deficiency: Causes

• Dietary deficiency
• Destruction of intestinal bacteria (due to antibiotics)
• Malabsorption of lipids
• Newborns (lack of gut colonization, placental transport)
• Medications (like warfarin)

Vitamin K Deficiency: Clinical Manifestations

• Hemorrhagic disease in newborns
• Post-traumatic bleeding
• Bruising tendencies
• Ecchymotic patches
• Mucus membrane hemorrhage

Lab Investigations for Vitamin K Deficiency

• Hypoprothrombinemia (low levels of prothrombin)
• Increased blood coagulation times
• Prolonged prothrombin time