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.


LECTURE OUTLINE :

Vitamins:
Definition:
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.





Transport:


  • 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.



Functions:


  • 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

K
Fibrin

(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.


Cancer:

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 :
PAEDIATRIC:

Hypoprothrombinemia:

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

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



NEONATE:

Treatment of severe hemorrhage disease:



  • 1 to 2 mg.


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