Explain in detail the absorption and biochemical role of vitamin K in the body. Add a note on the deficiency manifestations of vitamin K along with relevant laboratory investigations for confirmation.

Absorption of Vitamin K

Vitamin K absorption is a complex process dependent on efficient fat absorption. Dietary vitamin K (phylloquinone – K1 from plants, and menaquinone – K2 from bacteria and animal sources) is incorporated into micelles in the small intestine along with other dietary fats. These micelles are then absorbed by enterocytes. Within the enterocytes, vitamin K is packaged into chylomicrons, which are released into the lymphatic system and eventually enter the bloodstream. Bile salts are crucial for micelle formation, explaining why fat malabsorption syndromes often lead to vitamin K deficiency.

Biochemical Role of Vitamin K

The primary biochemical role of vitamin K is as a coenzyme for a carboxylase enzyme called γ-glutamyl carboxylase. This enzyme catalyzes the post-translational carboxylation of specific glutamic acid residues in several proteins, converting them to γ-carboxyglutamic acid (Gla) residues. These Gla residues are essential for calcium binding, enabling the proteins to function effectively.

Key Vitamin K-Dependent Proteins:

• Coagulation Factors: Factors II (prothrombin), VII, IX, and X require vitamin K for their activation. Carboxylation of these factors allows them to bind calcium ions, which is crucial for their interaction with phospholipid surfaces and subsequent participation in the coagulation cascade.
• Osteocalcin: This bone protein, produced by osteoblasts, requires carboxylation for calcium binding and plays a role in bone mineralization.
• Matrix Gla Protein (MGP): MGP inhibits vascular calcification by binding calcium in soft tissues and arterial walls.
• Gas6 Protein: Involved in the development and function of the nervous system.

Deficiency Manifestations of Vitamin K

Vitamin K deficiency manifests primarily as bleeding disorders. The severity of the bleeding depends on the degree of deficiency.

Clinical Presentations:

• Newborns: Hemorrhagic disease of the newborn (HDN) is a significant concern. Newborns have low vitamin K stores at birth, limited intestinal flora to synthesize K2, and breast milk is relatively low in vitamin K. This often presents as bleeding in the first few days of life. Prophylactic vitamin K injections are routinely administered to newborns to prevent HDN.
• Adults: Deficiency in adults is less common and usually associated with malabsorption syndromes (e.g., cystic fibrosis, celiac disease, Crohn's disease), prolonged antibiotic use (which disrupts gut flora), or certain medications (e.g., warfarin). Symptoms include easy bruising, nosebleeds, heavy menstrual bleeding, and gastrointestinal bleeding.
• Rare Manifestations: In severe cases, deficiency can lead to intracranial hemorrhage, which is life-threatening.

Laboratory Investigations for Confirmation

Several laboratory tests can confirm vitamin K deficiency:

Test	Principle	Interpretation
Prothrombin Time (PT)	Measures the time it takes for plasma to clot. Vitamin K-dependent factors are crucial for the coagulation cascade.	Prolonged PT indicates a deficiency in vitamin K-dependent factors.
International Normalized Ratio (INR)	Standardized PT result to account for variations in reagents and equipment.	Elevated INR suggests impaired coagulation due to vitamin K deficiency.
Factor Assays	Directly measures the levels of vitamin K-dependent coagulation factors (II, VII, IX, X).	Reduced levels of these factors confirm the deficiency.
Vitamin K Levels (Plasma)	Directly measures the concentration of vitamin K in plasma.	Low levels confirm deficiency, but this test is less commonly used due to technical challenges.

The PT/INR is the most commonly used initial screening test. A shortened correction of PT/INR after vitamin K administration (typically 1-2mg IV or IM) confirms the diagnosis.