Vitamin k and its Disorders Learning Objectives

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Vitamin K and its Disorders
Learning Objectives
The students should be able to :

  • Define vitamins.

  • Enlist the different types of vitamins.

  • Define fat soluble vitamin

  • Justify that the vitamins k acts as coenzymes with examples.

  • Give the clinical conditions associated with the deficiency of vitamin k.


Vitamins are a group of organic nutrients, required in small quantities for a variety of biochemical functions.

  • The discovery of the first vitamin was published in 1911 by a Polish biochemist, Casimir Funk.

  • The term vitamine is derived from the words vita (meaning life giving) and amine (were originally thought to be amines).

  • Usually only a few milligrams (mg) or micrograms (μg) are needed per day, but these amounts are essential for health.

Types of vitamins:

  1. Water soluble :

  1. Vitamin B1(thiamine)

  2. Vitamin B2(Riboflavin)

  3. Niacin

  4. Vitamin B6(pyridoxine)

  5. Vitamin B12 (cobalamin)

  1. Pantothenic Acid.

  2. Vitamin C

  3. Biotin and folic acid

  1. Lipid soluble:

  1. Vitamin A

  2. Vitamin D

  3. Vitamin E

  4. Vitamin K

Most vitamins cannot be synthesized by the body, so have to be provided by the diet.

    • An exception is vitamin D which can be obtained from cholesterol by the action of sunlight on the skin.

    • Small amounts of a B vitamin (niacin) can be made from the essential amino acid, tryptophan.

    • Vitamin K is formed by bacterial action in the large intestine.

Vitamin K (phylloquinone) :

  • Vitamin K is named anti hemorrhagic vitamin.

  • Vitamin K is found in foods from both plant and animal sources and is also made by bacteria in the gut.

  • RDA: 80 µg for men, 65 µg for women.

Vitamin K – Sources :

  • Bacteria in the large intestine (10-15%)

  • Plant sources

    • Green leafy vegetables

    • Some oils

    • Cauliflower

    • Broccoli

    • tomatoes

  • Animal sources

    • Liver

    • Milk.

Transport:__Absorption_depends_on_form'>Absorption, Transport:
Absorption depends on form:

  • Phylloquinone (K1)

    • Plant sources.

  • Menaquinone (K2)

    • Bacteria.

  • Menadione (K3)

    • Synthetic.


  • In the intestinal cell → chylomicron → lymph → blood → tissue.

Vitamin K:

  • The coagulation vitamin

  • Exists in 2 forms:

    • plant origin: phylloquinone or vitamin K1

    • bacterial origin: menaquinones or vitamin K2

  • Also certain synthetic quinones have vitamin K activity

    • Menadione (vitamin K3)

    • Menadiol sodium phosphate (vitamin K4).

Forms of Vitamin K:

  • K1, phylloquinone

    • Chloroplasts in plants

  • K2, menaquinone

  • K3, menadione

    • Synthetic, water soluble form

    • Complexed to improve stability.

Vitamin K1:

  • Phylloquinone: found in dairy products, green vegetables, and vegetable oils, are an aqueous, colloidal solution of vitamin K1.

    • Phytomenadione.

    • Phytonadione.

    • Phytylmenadione.

    • 3-Phytylmenadione.

    • Phytylmenaquinone.

Vitamine K2:

  • Menaquinone, which is synthesized by gut flora.

    • Menatetrenone

    • MK4

    • Vitamin K2(20)

    • Vitamin MK4.

Vitamin K 3:

  • Menadione: It is a synthetic, water soluble form that is no longer used medically because of its ability to produce hemolytic anemia.

    • Menadione

    • Menadione sodium bisulfite

    • Menadiol

    • Menadiol sodium phosphate

    • Menadiol sodium phosphate hexahydrate .

Vitamin K 4:

  • Acetomenaphthone.


  • Synthesis of proteins involved in hemostasis.

  • Coenzyme for gamma glutamyl carboxylase

    • Post translationally modifies specific precursor proteins.

    • Clotting factor VII,IX,X and Prothrombin.

    • Vitamin K dependent proteins.

  • Osteocalcin (Role In Bone Metabolism)

  • Protein C,S,Z

  • CHD prevention

  • Vitamin K is the only fat soluble vitamin which acts as coenzyme.

Role of Vitamin K in coagulation:

Vitamin K:

  • Clotting factors VII, IX, and X and prothrombin (II) all require carboxylation of glutamate residues for functional activity

    • Anticoagulant coumadin is a Vitamin K antagonist.

  • Activation of anticoagulant proteins C and S also requires glutamate carboxylation.

Role of Vitamin K in Homeostasis:

  • Clotting factors are synthesized in the liver as inactive precursors - vitamin K converts them to their active forms

    • Conversion of prothrombin to thrombin, an active enzyme

    • Formation of fibrinogen to fibrin, leading to clot formation

  • Stimulates bone formation and decreases bone resorption.

Role of Vitamin K & Ca++ in Coagulation :

  • Posttranslational modification requires carboxylation of glutamate residues for functional activity.

  • Gamma Carboxylation residues enhance Ca++ binding by clotting factor.

  • This Ca++ binds with Phospholipids in plasma membrane.

Blood-Clotting Process:

Vitamin K Calcium & thromboplastin Fibrinogen

(a phospholipid) from (a soluble protein)

blood platelets

Several precursors Prothrombin Thrombin

earlier in the series (an inactive protein) (an active enzyme)

depend on vitamin


(A solid clot)

Function and Mechanism :
Blood Clotting:
A deficiency of vitamin K results in an increase in prothrombin time. The usual clinical manifestation is a tendency to hemorrhage.

Vascular Disease:
Vascular smooth-muscle cells and arterial intima synthesize a matrix protein that undergoes a vitamin K-dependent carboxylation to become matrix gammacarboxyglutamic acid protein (MGP).
Glucose Control:

The pancreas, which makes insulin, is a site of synthesis

for certain vitamin K-dependent proteins.

Bone Activity:

Higher vitamin K status has been associated with lower fracture risks.


Anticarcinogenic activities of vitamin K have been observed in various cancer cell lines, including prostate cancer cells.

Vitamin K Cycle:
- Vitamin KH2 is active form and K epoxide inactive form.

  • Dicoumarol and warfarin are antagonists of vitamin K.

  • Dicoumarol found in moldy sweet clover

    • Sweet clover disease

  • Warfarin

    • Rat poison.

Why is newborn Vitamin K deficient ?

  • Maternal: cord blood ratio—30:1

  • Hepatic content in neonate-25% of adult.

  • Human milk content (2-15ug/l)-25% cow milk.

  • Colostrum rich in Vitamin K not given.

  • Sterile gut.

  • Plasma half-life-72 hrs.

Vitamin K:
Who are at great risk of vitamin k deficiency?

    • Infants

Deficiency symptoms are:

  • Easy bruising

  • Increase Clotting time

  • Bleeding gums and nose bleed.

Vitamin K – Deficiency:

  • Primary deficiency rare;

  • secondary deficiency occurs when fat absorption is impaired (e.g., cystic fibrosis, Crohn’s disease) or following long-term or high-dose administration of antibiotics (they kill the bacteria in large intestine)

  • Prolonged clotting time

    • Generalized hemorrhages.

Causes of Vitamin K Deficiency:

    • Fat malabsorption.

    • Reduced gut bacterial flora.

  • Administration of wide spectrum antibiotics.

  • neonatal period before gut is colonized

    • Liver disease with reduced recycling of vitamin K.

Effects of vitamin K deficiency:

    • Bleeding diathesis.

    • Estimated 3% prevalence of vitamin K-dependent bleeding diathesis among neonates warrants routine prophylactic vitamin K therapy for all newborns.

Vitamin K – Toxicity:

  • Not common except with over-supplementation

    • Phylloquinone and menaquinone are relatively nontoxic

  • Jaundice; brain damage.

    • Menadione toxic to skin and respiratory tract in high doses.

  • Menadione Toxicity :

    • Liver damage.

    • Infants supplemented.

  • Hemolytic anemia.

  • Hyperbilirubinemia.

  • Severe jaundice.

Dose of Vitamin K1 :


  • Infants: 1 to 2 mg q4-8 hours as required.

  • Children: 2.5 to 10mg q6-8 hours as required.


Treatment of severe hemorrhage disease:

  • 1 to 2 mg.

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