Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Vitamin K Lecture PPT
VITAMIN K
? "K " is the abbreviation of the German word
"Koagulation "
? Anti-hemorrhagic factor
? Specific coenzyme function required for coagulation
? VITAMIN K are Naphthoquinone derivatives and
have long side Isoprenoid chain.
? 1929 ? Henrick Dam ? isolation of Vitamin K1 ?(Noble
Prize )
? 1939 ? Edward Doisy ? isolation of Vitamin K2 ?(Noble
Prize 1943 )
Vitamin K- Chemistry
? Vitamin K represents a group of lipophilic and
hydrophobic vitamins.
? Three compounds have the biological activity of
vitamin K
? Phylloquinone (Vitamin K1), the normal dietary
source, found in green vegetables
? Menaquinones (vitamin K2), synthesized by
intestinal bacteria, with differing lengths of side
chain; and
? Menadione and menadiol diacetate, synthetic
compounds that can be metabolized to phylloquinone
Vitamin K are naphthoquinone
derivatives
.
.
ABSORPTION
? Absorption takes place in intestine in the
presence of bile salts.
? The transportation from intestine is carried out
through chylomicrons.
? Storage occurs in liver
? Transportation from liver to peripheral cells is
carried out bound with beta lipoproteins.
Biochemical Functions of vitamin K
? Vitamin K act as a coenzyme for the
carboxylation of glutamic acid residues present in
the protein and this reaction is catalyzed by a
carboxylase (microsomal)
? Although
vitamin
K-dependent
gamma-
carboxylation occurs only on specific glutamic
acid residues in a small number of vitamin K-
dependent proteins, it is critical to the calcium-
binding function of those proteins
.
? It involves the conversion of glutamate (Glu)
to -carboxyglutamate (Gla) and requires
vitamin K,O2 and CO2
? The formation of - carboxyglutamate is
inhibited by dicumarol, an anticoagulant found
in spoilt sweet clover
? Warfarin is a synthetic analogue that can
inhibit vitamin K action
.
(Glu)
(Gla)
Vitamin K cycle
? Vitamin K is a fat-soluble vitamin, the body
stores very little of it, and its stores are rapidly
depleted without regular dietary intake.
? Because of its limited ability to store vitamin
K, the body recycles it through a process called
the vitamin K cycle.
? The vitamin K cycle allows a small amount of
vitamin K to function in the gamma-
carboxylation of proteins many times,
decreasing the dietary requirement.
Quinone
DICUMAROL
.
? Vitamin K hydroquinone (active form) is oxidized
to the Epoxide form during the process of
enzymatic reaction.
? The initial form (hydroquinone form) is
regenerated by two steps process.
? Vitamin K Epoxide is reduced to the quinone by a
Epoxide reductase, and
? the quinone is reduced to the active hydroquinone
by
--either the same reductase or
---by a vitamin K reductase(quinone reductase).
...Role In Clotting
? The functions of vitamin K are concerned with
blood clotting process.
? The clotting factors II, VII, IX and X are
synthesized as inactive precursors in the liver.
? Vitamin K brings about post-translational
modification i.e. carboxylation of glutamic
acid residues of these blood clotting factors.
.
? - Carboxyglutamic acid (Gla) residues of
clotting factors are negatively charged (COO-)
and they combine with positively charged
calcium ions (Ca2+) to form a complex
? The complex binds to the phospholipids on the
membrane surface of the platelets.
? Leads to increased conversion of prothrombin
to thrombin
OTHER FUNCTIONS
? Vitamin K is also important in synthesis of two
proteins that contain -carboxyglutamate that
are present in bone-
1. Osteocalcin and
2. Bone matrix Gla protein.
1. Osteocalcin is a protein synthesized by
osteoblasts.
? The synthesis of osteocalcin by osteoblasts is
regulated by the active form of vitamin D,
1,25(OH)2D3 or calcitriol. .
? The mineral-binding .capacity of osteocalcin
requires
vitamin
K-dependent
gamma-
carboxylation of three glutamic acid residues
? After gamma carboxylation osteocalcein binds
tightly to calcium.
? Osteocalcin also contains hydroxy proline, so
its synthesis is dependent on both vitamins K
and C; in addition, its synthesis is induced by
vitamin D.
? The release into the circulation of osteocalcin
provides an index of vitamin D status.
.
2.Matrix Gla protein- .
? MGP has been found in bone, cartilage, and soft
tissue, including blood vessels.
? MGP prevents the calcification of soft tissues and
cartilages, while facilitating normal bone growth
and development
3. Protein S-
? The vitamin K-dependent anticoagulant protein S
? Children with inherited protein S deficiency suffer
complications related to increased blood clotting
as well as decreased bone density.
.
4. Nephrocalcin in kidney
5. Product of the growth arrest specific gene
(Gas6)- which is involved in both the
regulation and differentiation and development
of nervous system, and control of apoptosis in
other tissues.
6. Vitamin K is required for ETC and oxidative
phosphorylation
- Vitamin K antagonists such as dicumarol act
as uncouplers of oxidative phosphorylation
Vitamin K deficiency
Causes
? Lack of vitamin K in the diet
? Fat malabsorption
? Disease or surgical interventions that affect the
ability of intestinal tract to absorb vitamin K
? Chronic liver diseases
? Prolonged use of oral antibiotics
? Prolonged use of Warfarin
.
? Pre mature infants and new born babies
- Transplacental transfer of vitamin K is very
limited during pregnancy,
-The storage of vitamin K in neonatal liver is
also limited.
- Breast milk is a poor source of vitamin K.
- newborn infants to mother with poor vitamin
K stores
Deficiency manifestations
? The main symptom is bleeding (hemorrhage)
--into the skin (causing bruises),
--from the nose,
--from a wound,
---in the stomach, or
---in the intestine.
? Blood may be seen in the urine or stool.
? Having a liver disorder increases the risk of
bleeding because clotting factors are made in
the liver.
? Vitamin K deficiency may also weaken bones.
.
? In newborns, life-threatening bleeding within
or around the brain may occur.
? Intracranial hemorrhage can occur during the
delivery process and can lead to severe
complications.
? Soft tissue hemorrhages may be there.
A deficiency of vitamin K can lead to extreme bleeding,
which can begin as a gum or nose discharge or bruising
Diagnosis
? A prolonged Prothrombin Time (PT) in the
absence of liver disease is usually the first
laboratory test result to be abnormal in vitamin
K deficiency bleeding.
? Prothrombin time is measured before and after
giving vitamin K in situation of doubt. If it
returns to normal after vitamin K injection, it
suggests vitamin k deficiency and rules out
liver diseases. If not, liver disease is the likely
cause.
.
? Clotting Time
The clotting time is usually between 6-8 minutes.
It is also increased in vitamin K deficiency
RDA
ADULTS - 50-100 g/day
SOURCES
? Vitamin K is found in green leafy vegetables
such as kale and spinach
? Appreciable amounts are also present in
margarine and liver.
? Vitamin K is present in vegetable oils and is
particularly rich in olive, canola, and soybean
oils.
? Some amount is contributed by intestinal
bacteria
Prevention
? A vitamin K injection in the muscle is
recommended for all newborns to reduce the
risk of bleeding within the brain after delivery
? Intramuscular (IM) vitamin K prophylaxis at
birth is the standard of care.
? These measures have served to make vitamin
K deficiency bleeding a rarity.
Hypervitaminosis K
? Large dose (>5 mg) of menadione can cause
toxicity.
? Hypervitaminosis K leads to
1. Hemolytic anemia
2. Jaundice ( hyperbilirubinemia and
kernicterus-leading to brain damage
This post was last modified on 30 November 2021