Download Vitamin K and its Disorders

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.
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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:
A. Water soluble :
a)
b)
c)
d)
e)
f)
g)
h)
Vitamin B1(thiamine)
Vitamin B2(Riboflavin)
Niacin
Vitamin B6(pyridoxine)
Vitamin B12 (cobalamin)
Pantothenic Acid.
Vitamin C
Biotin and folic acid
B. Lipid soluble:
a)
b)
c)
d)
Vitamin A
Vitamin D
Vitamin E
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.
Absorption, Transport:
Absorption depends on form:
 Phylloquinone (K1)
– Plant sources.
 Menaquinone (K2)
– Bacteria.
 Menadione (K3)
– Synthetic.
 Absorption occurs as part of micelles thus enhanced by
fat, bile salt, pancreatic juice.
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
– Bacterial synthesis
 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
Several precursors
earlier in the series
depend on vitamin
K
Calcium & thromboplastin
Fibrinogen
(a phospholipid) from
(a soluble protein)
blood platelets
Prothrombin
(an inactive protein)
Thrombin
(an active enzyme)
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)
– Newborn babies with sterile GI tract;
– single vitamin K dose given to prevent hemorrhage
 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.