2. collective name for all stereoisomers of
tocopherols and tocotrienols
8 related fat soluble substances with Vit E activity
Most imp dietary form - α-tocopherol
Rich: sunflower oil
Important: vegetables, nuts, seed oils ,meats,
cereal grains
No RNI.
Safe intake 4mg (M), 3mg (F)
3. Direct metabolic actions:
efficient pyroxyl radical scavenger that protects
LDLs & PUFA in cell membranes from oxidation
by free radicals
Maintains cell membrane structure
DNA synthesis and signalling
Anti-inflammatory and immune systems:
inhibits prostaglandin synthesis and the
activities of protein kinase C
and phospholipase A2.
4. After absorption, vitamin E is taken up from
chylomicrons by the liver, and a hepatic -
tocopherol transport protein mediates
intracellular vitamin E transport and
incorporation into very low density
lipoprotein (VLDL).
5. severe and prolonged malabsorptive diseases
-celiac disease, or after small-intestinal
resection.
Children with cystic fibrosis or prolonged
cholestasis -areflexia and hemolytic anemia.
Children with abetalipoproteinemia cannot
absorb or transport vitamin E
A familial form of isolated vitamin E deficiency
-defect in tocopherol transport protein.
6. causes axonal degeneration of the large
myelinated axons and results in posterior
column and spinocerebellar symptoms.
7. Clinical Finding
•Peripheral neuropathy -areflexia, ataxic
gait, and decreased vibration and position
sensations.
• Ophthalmoplegia, skeletal myopathy, and
pigmented retinopathy
•mild hemolytic anemia, visual scotomas
8. low blood levels of α-tocopherol (<5 g/mL,
or <0.8 mg of α-tocopherol per gram of total
lipids)
9. Symptomatic : 800–1200 mg of α-tocopherol
per day.
Abetalipoproteinemia : 5000–7000 mg/d.
Children with symptomatic deficiency :
400 mg/d orally of water-miscible esters;
alternatively, 2 mg/kg per d may be
administered intramuscularly.
10. Vitamin E in high doses may
protect against oxygen-induced
retrolental fibroplasia and
bronchopulmonary dysplasia as
well as intraventricular
hemorrhage of prematurity.
suggested to treat intermittent
claudication, and slow the aging
process,
in combination with other
antioxidants may help prevent
macular degeneration.
High doses (60–800 mg/d) have
been shown in controlled trials to
improve parameters of immune
function and reduce colds in
nursing home residents
11. High doses of vitamin E (>800 mg/d) may
reduce platelet aggregation and interfere with
vitamin K metabolism
contraindicated in patients taking warfarin
and antiplatelet agents (such as aspirin or
clopidogrel).
Nausea, flatulence, and diarrhea reported at
doses >1 g/d.
12. two natural forms of vitamin K
No RNI
Safe intake: 1 µg/kg
In diet-
Vit K 1- phylloquinone: from green
vegetables, oils- olive, canola, soya
,margarine and liver
Vit K 2- menaquinone: from fermented
products, synthesized by bacterial flora in
colon and found in hepatic tissue
13. posttranslational carboxylation of glutamic acid, production
of γ-carboxyglutamate(gla) which is necessary for calcium
binding to γ-carboxylated proteins –
Functions
14. •coagulation factor proteins- II, VII, IX, X ( to bind
to phospholipid surfaces)
•protein C, protein S
•Osteocalcin and matrix
gla protein important for
bone mineralization
•Warfarin-type drugs
inhibit –carboxylation
15. <10 g/d
Fat malabsorption
chronic small-intestinal disease (e.g., celiac
disease, Crohn's disease),
obstructed biliary tracts,
after small-bowel resection.
Broad-spectrum antibiotic treatment -by
reducing gut bacteria, and by inhibiting the
metabolism of vitamin K.
liver disease - primary biliary cirrhosis
18. particularly susceptible because
low fat stores,
low breast milk levels of vitamin K
sterility of the infantile intestinal tract,
liver immaturity,
poor placental transport.
Intracranial bleeding, as well as gastrointestinal
and skin bleeding, can occur in vitamin K–
deficient infants 1–7 days after birth.
Thus, vitamin K (1 mg IM) is given
prophylactically at the time of delivery.
19. Prolonged Prothrombin Time (PT)
the most common and earliest finding
Prolonged aPTT and PT
reduced clotting factors
may also be measured directly by HPLC.
20. parenteral dose of 10 mg- restores normal levels of
clotting factor within 8–10 h.
chronic malabsorption- 1–2 mg/d of vitamin K orally,
or 1–2 mg/week parenterally.
ongoing bleeding or a need for immediate correction
before an invasive procedure- replacement with FFP or
PCC
The latter should be avoided in patients with severe
underlying liver disorders due to high risk of
thrombosis.
Reversal of excessive anticoagulant therapy with
warfarin or warfarin-like drugs -1 mg orally or by
intravenous injection) for asymptomatic patients.
21. Life-threatening bleeds:
the use of recombinant factor VIIa in nonhemophilia
patients on anticoagulant therapy has been shown to
be effective at restoring hemostasis rapidly, allowing
emergency surgical intervention.
However, patients with underlying vascular disease,
vascular trauma and other comorbidities are at risk for
thromboembolic complications that affect both
arterial and venous systems
Thus, the use of factor VIIa is limited to
administration of low doses given for only a limited
number of injections.
Close monitoring for vascular complications.
22. combined deficiency of all vitamin K–
dependent proteins, including the
procoagulant proteins II, VII, IX, and X and
the anticoagulant proteins C and S.
Mutations in the genes encoding the
gammaglutamyl-carboxylase (GGCX) or
vitamin K epoxide reductase complex 1
(VKORC1) result in defective enzymes and
thus in vitamin K–dependent factors with
reduced activity(1 to 30% of normal)
mild to severe bleeding episodes present
from birth.
high doses of vitamin K. severe bleeding-
FFP or PCC
23. not been described
High doses can impair the actions of oral
anticoagulants.
Hinweis der Redaktion
, although only the RR tocopherols meet human requirements.
RDA for vitamin E is 15 mg/d
A network of other antioxidants (e.g., vitamin C, glutathione) and enzymes maintains vitamin E in a reduced state.
The transport protein has particular affinity for the RRR isomeric form of -tocopherol; thus, this natural isomer has the most biologic activity.
Either vitamin E or selenium deficiency in the host has been shown to increase certain viral mutations and, therefore, virulence.).
but intervention studies using vitamin E to prevent cardiovascular disease or cancer have not shown efficacy, and at doses >400 mg/d, vitamin E may even increase all-cause mortality rates.
Phylloquinone can be converted to menaquinone in some organs.
by preventing the conversion of vitamin K to its active hydroquinone form.
In patients with warfarin therapy, the antiobesity drug orlistat can lead to international normalized ratio (INR) changes due to vitamin K malabsorption.
due to hemorrhage
Pt- 2,7,9,10 ptt-2 FVII has the shortest half-life among these factors that can prolong the PT before changes in the aPTT
Patients with liver disease may have an elevated prothrombin time because of liver cell destruction as well as vitamin K deficiency. If an elevated prothrombin time does not improve on vitamin K therapy, it can be deduced that it is not the result of vitamin K deficiency.
