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2. Raw or minimally cooked (vit.C lengvai oksiduojasi) vegetables
METABOLISMvit. C is not metabolized.
šalinasi su šlapimu.
FUNCTIONS- strong reducing agent - reversibly oxidized and reduced, functions as REDOX SYSTEM in cell:
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ENDOCRINE SYSTEM, METABOLISM: Vitamins
1. Activates HYDROXYLASES that hydroxylate Pro and Lys in procollagen - helps maintain integrity of substances of mesenchymal origin (connective tissue, osteoid tissue, dentin) - essential for wound healing and recovery from burns.
2. Metabolism of Phe and Tyr (synthesis of catecholamines) – DOPAMINE β-HYDROXYLASE
3. Facilitates iron absorption (redukuoja Fe3+ į Fe2+).
5. Cold or heat stress - increased urinary excretion.
PATHOLOGYDefective formation of intercellular cement substances (in connective tissues, bones, dentin):
1) weakened capillaries → hemorrhage
2) defects in bone and related structures; endochondral growth ceases (osteoblasts fail to form osteoid tissue), instead, fibrous union forms between diaphysis and epiphysis, costochondral junctions enlarge (“scorbutic rosary” ≈ in rickets).
3) hemorrhagic areas are organized avascularly, so that wounds heal poorly and break open easily.
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SYMPTOMS & SIGNS
Latent period 3-6 months.
Pradžioje - lassitude, weakness, irritability, weight loss, vague myalgias and arthralgias.
Overt scorbutic symptoms:
1. Pirmasis simptomas - spontaneous hemorrhages in any part of body.
patognomiška - hyperkeratotic hair follicle with surrounding hyperemia (perifolliculitis), perifollicular petechiae and ecchymoses esp. in lower limbs).
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multiple splinter hemorrhages may form crescent near distal nail end (more extensive than those in bacterial endocarditis).
2. Bleeding gums - gums become swollen (hyperplastic), purple, spongy, and friable; they bleed readily (gingivitis).
secondary infection, gangrene, and teeth loosening eventually occur.
3. Old scars break down, new wounds do not heal.
4. Bone lesions do not occur in adults!
vaikams džn. kartu esti ir vit.D hipovitaminozė → osteopathia hemorrhagica infantum (s. scurvy rickets).
5. Arthritis resembling RA (due to bleeding around or into joint)
6. Heart failure, inanition and debility.
Negydant – mirtis!
see 2733 (4a) p.
LABORATORY DIAGNOSIS1. [Ascorbic acid]↓:
a) in plasma2733 (7)
ENDOCRINE SYSTEM, METABOLISM: Vitamins
b) more significant in WBC-platelet layer of centrifuged blood.
c) when vit. C stores are depleted, little appears in urine after test dose of vitamin C.
2. Positive capillary fragility test
3. Anemia (hypochromic, normocytic or microcytic)
Bleeding and coagulation times are normal!
PROPHYLAXISVitamin C 60 mg/d is fully protective!
Huge doses of vitamin C (≈ 10 g/d):
a) neapsaugo nuo common cold, neįtakoja progress of malignant disease or atherosclerosis.
b) acidify urine (vit. C stipri rūgštis) - predispose to urinary calculi from oxalate.
c) diarrhea from osmotic effects.
d) promote iron overload.
TREATMENTIn adults, ascorbic acid 300-500 mg/d for 2 wk or until signs have disappeared.
signs and symptoms usually disappear over 1-2 wk.
BIOTIN (VITAMIN H)
RDAunknown (30-100 μg?)
SOURCES intestinal m/o susintezuoja pakankamus kiekius , todėl dietary source is normally not necessary.
dietary sources: liver, egg yolk, yeast.
METABOLISMBiotin is not modified.
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ENDOCRINE SYSTEM, METABOLISM: Vitamins
Biotin functions as prosthetic group:
biotin holocarboxylase synthetase kovalentiškai prijungia biotiną prie apoenzimo.
biotinidase removes biotin from apoenzyme (during protein turnover) and allows biotin to be recycled.
FUNCTIONSBiotin is carrier of CO2 in carboxylation reactions.
Four CARBOXYLASES require biotin (amino acid and fatty acid metabolism, gluconeogenesis):
90% turi būti gaunama su maistu: cereals, meat, yeast, etc. Termostabilus.
METABOLISM & FUNCTIONSNiacin is precursor for NAD + and NADP + - coenzymes for DEHYDROGENASES (oxidation-reduction reactions) – vital in cell metabolism!
PELLAGRA
ETIOLOGYPrimary deficiency - in areas where maize (Indian corn) forms major part of diet:
– bound niacin, found in maize, is not assimilated in intestinal tract unless it has been previously treated with alkalis (as in preparation of tortillas).
– corn protein is deficient in tryptophan.
Secondary deficiency:
isoniazid therapy (drug replaces niacinamide in NAD)
alcoholism - combination of decreased intake, impaired absorption and utilization, increased requirements, and possibly apoenzyme defect!
frequent, long-term, or highly concentrated dextrose infusions, coupled with low thiamine intake, may precipitate thiamine deficiency!
PATHOLOGYNeural changes:
– axon loss in peripheral nerves, particularly of legs (distal segments are affected earliest and most severely).
– degeneration can occur in all tracts and columns of spinal cord.
– hemorrhagic polioencephalitis in severe deficiency.
Heart is dilated and enlarged.
Vasodilation occurs and can result in some edema before frank high-output heart failure occurs.
SYMPTOMS & SIGNS
WET BERIBERI - high output cardiac failure with vasodilation and warm extremities.
see 2733 (8a) p.
DRY BERIBERI - bilateral symmetric polyneuropathy (as in alcoholics!!!): see Psy21 p.
– predominantly lower extremities, distal parts - severe burning dysesthesias, sensory loss, weakness and wasting, trophic changes (shiny skin, hair loss), early absent ankle jerks!
– arms may be affected after legs.
CEREBRAL BERIBERI (WERNICKE-KORSAKOFF SYNDROME)
CNS changes result from severe acute deficiency superimposed on chronic deficiency:
Korsakoff syndrome – amnesia → confusion, confabulations; see S6 p.
Wernicke syndrome – ataxia, ophthalmoplegia. see Psy21 p.
LABORATORY DIAGNOSISa) serum [thiamine] lacks sufficient sensitivity and specificity to be used alone.
b) blood pyruvate and lactate↑
c) 24-hour urinary excretion of thiamine↓
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d) RBC transketolase activity↓ - most accurate indicator of tissue stores! (increases after TPP administration - TPP effect)
e) therapeutic trial of thiamine :
panašias polineuropatijas sukelia diabetas ir alkoholizmas, bet jos do not respond to thiamine.
heart failure responds poorly to digitalis or diuretics; therapeutic trial of thiamine → edema and congestion respond in few hours!
PROPHYLAXIS- su gliukozės infūzijomis kartu skirti tiaminą (iki 100 mg i/v, nes netoksiškas – perteklius lengvai pasišalina su šlapimu) – ypač esantiems neaiškios kilmės komoje.
TREATMENTNegydant mirtis Recovery from neurologic deficits is often incomplete!
thiamine up to 100-200 mg/d parenteraliai + turtinga dieta.
dažnai lydi other B-complex deficiencies, and multiple water-soluble vitamin therapy at 5-10 times RDA is advisable for several weeks.
magnesium (cofactor for transketolase) - to correct thiamine resistance and frequently accompanying hypomagnesemia.
hyponatremia should be corrected slowly (rapid correction may cause central pontine myelinolysis).
At present, there is no generally accepted test of vitamin B6 status!
CSF and plasma [pyridoxal-5-phosphate] may be more precise method of confirming diagnosis of pyridoxine dependency.
PROPHYLAXIS- vit. B6 skyrimas (100 mg/d) vartojant jam antagonistinius vaistus.
TREATMENTUnderlying causes should be corrected.
Pyridoxine:
deficiency in adults - 50-100 mg/d per os.
dependency - lifelong oral pyridoxine up to 10-600 mg/d.
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pyridoxine-dependent seizures – start with 100-200 mg/d IV with simultaneous EEG → seizures will abruptly cease, and EEG will normalize during next few hours.
N.B. seizures are particularly resistant to anticonvulsants!
VITAMIN B6 TOXICITY
- pyridoxine megadoses (2-6 g/d for months), mistakenly taken for premenstrual tension.
very severe sensory neuropathy - propriorecepcijos sutrikimai kojose, sensory ataxia (gali būti negrįžtama* net nutraukus piridoksino vartojimą!).
*irreversibly damaged dorsal root ganglion cells
RETINOL (VITAMIN A)
RDA1000 μg (3000 IU) retinol equivalents
1 retinol equivalent = 1 μg retinol = 6 μg β-carotene = 3 IU = 3 USP U
SOURCESProvitamins (carotenes):
dark green leafy vegetables
yellow vegetables (carrots)
red palm oil
Vitamin A:
1) fish liver oil
2) liver
3) egg yolk
4) fortified milk, margarine
METABOLISM
Vitaminas A yra alkoholis – RETINOL
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Vitamino A aldehidas – RETINAL
maiste randami CAROTENES (s. provitamin A carotenoids) - class of carotenoids.
carotenes esti trijų rūšių, jiems skylant žarnyne susidaro RETINAL:
β-carotene skyla į dvi RETINAL molekules
α-carotene ir γ-carotene duoda tik po vieną RETINAL molekulę.
žarnyno epiteliocituose :
RETINAL redukuojamas į RETINOL
RETINOL is re-esterified with palmitate (RETINYL PALMITATE – pagrindinė sandėliavimo forma) ir keliauja į kepenis.
kepenyse esti 90% vit.A atsargų (as retinyl palmitate).
kraujyje retinol transportuojamas susijungęs su retinol binding protein.
FUNCTIONSA. Role in vision:
in retinal rod cells, retinol oksiduojamas į retinal.
11-cis RETINAL izomeras jungiasi (as prosthetic group) su scotopsin į regos pigmentą RHODOPSIN.
šviesos poveikyje 11-cis retinal virsta į all-trans RETINAL ir generuojamas veikimo potencialas.
smulkiau žr. 3536 p. (in EYE)
B. Kitos funkcijos : in somatic cells, retinol is converted to RETINOIC ACID, which combines with receptors that bind to DNA and regulate gene expression - regulation of epithelial growth, reproduction.
synthetic vitamin analogs (RETINOIDS) are used increasingly in dermatology (globular acne treatment).
possible protective role of β-carotene, retinol, and retinoids against some epithelial cancers is under investigation.
ISOTRETINOIN (13-cis-retinoic acid) skiriamas nėščioms sukelia malformations
DEFICIENCY2733 (20)
ENDOCRINE SYSTEM, METABOLISM: Vitamins
ETIOLOGYPRIMARY DEFICIENCY - endemic in areas, where rice, devoid of carotene, is staple (southern and eastern Asia).
SECONDARY DEFICIENCY:
inadequate conversion of carotene to vitamin A
interference with absorption, storage, or transport of vitamin A.
SYMPTOMS & SIGNS pathognomonic changes are confined to eye : see 2733 (13a) p.
1) night blindness (nyctalopia); užsitęsus hipovitaminozei atsiranda negrįžtami struktūriniai tinklainės pakitimai → aklumas.
2) xerophthalmia → keratomalacia* → ulceracija ir, prisidėjus infekcijai, perforacija → aklumas. *ragena praranda skaidrumą (reversible on vit. A treatment)
3) BITOT spots (superficial foamy patches composed of epithelial debris and secretions on bulbar conjunctiva).
keratinization of lung, GI tract, and urinary tract epithelia, follicular hyperkeratosis of skin.
gonadal dysfunction in males, miscarriage in females.
growth retardation in children.
In severe deficiency in children, mortality can be > 50%!
LABORATORY DIAGNOSISplasma [retinol] falls after liver stores are exhausted.
trial with therapeutic doses of vitamin A.
PROPHYLAXISXerophthalmia is major cause of blindness among children in most developing countries!
H: prophylactic doses of 66,000 µg (200,000 IU) of vitamin A palmitate in oil orally once every 3-6 mo for all children aged 1-4 yr; dose is halved for those < 1 yr.
TREATMENT
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oral vitamin A palmitate in oil 20,000 µg (60,000 IU) daily for 2 days and once before discharge from hospital after 7 to 10 days is usually effective.
in presence of vomiting or malabsorption, water-miscible vitamin A must be given IM (oil preparations are not used IM).
prolonged daily administration of large doses, especially to infants, must be avoided because toxicity may result!
During pregnancy and lactation, prophylactic or therapeutic doses should not exceed two times RDA to avoid possible damage to fetus!
VITAMIN A TOXICITY
ETIOLOGY1. Massive doses of vitamin A or its metabolites given for globular acne (although treatment is
effective, it puts patient at risk for vitamin A toxicity).
2. Arctic explorers ingesting several million units of vitamin A in polar bear or seal liver.
Excessive ingestion of carotene does not cause vitamin A toxicity (carotene is metabolized to vitamin A at slow rate) but produces CAROTENEMIA - asymptomatic but may lead to CAROTENOSIS, in which skin (but not sclera!!!) becomes deep yellow, especially on palms and soles.
SYMPTOMS & SIGNSAcute toxicity:
1) increased ICP (pseudotumor cerebri): headache and vomiting; may lead to death unless ingestion is discontinued.
2) rash and peeling of skin
Chronic toxicity:
1) hepatosplenomegaly, ascites
2) bone thickening (cortical hyperostosis)
3) dermatosis
4) birth defects have been reported in children of women receiving 13-cis-retinoic acid (isotretinoin) for skin conditions during pregnancy!
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LABORATORY DIAGNOSIS- fasting plasma [retinol]↑
TREATMENTstopping vitamin A ingestion.
TOCOPHEROL (VITAMIN E) VITAMIN E (TOCOPHEROL) - generic term for compounds that have biologic activity of α-
tocopherol.
vitamin E group contains α-, β-, γ-, and δ-tocopherols.
d-α-tocopherol is only naturally occurring stereoisomer and most potent (1.49 IU/mg).
international standard is dl-α-tocopherol acetate (1.0 IU/mg).
RDA8-10 mg (30 IU)
SOURCES- vegetables, seed oil.
METABOLISM- unmetabolized in body; transported in VLDL molecule.
FUNCTIONS- scavenger of free radicals (i.e. antioxidant) - prevents peroxidation of polyunsaturated fatty acids in cellular membranes.
DEFICIENCY
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ETIOLOGY
INFANTS are born in state of relative vitamin E deficiency (the smaller and more premature infant, greater degree of deficiency) - limited placental transfer of vitamin E and rapid growth.
prophylactic vitamin E may prevent retinopathy of prematurity.
CHILDREN & ADULTS (adults have large vitamin E stores in adipose tissue!):
I. Vit. E transport defects:
1) abetalipoproteinemia (Bassen-Kornzweig syndrome) - mutation of microsomal triglyceride transfer protein (MTP) see 789 p., Mov50 p.
2) ataxia with isolated vitamin E deficiency (AVED) - 8q13 mutation of α-tocopherol transport protein (α-TTP) see Mov50 p.
II. Fat malabsorption :
chronic cholestatic diseases
celiac disease
SYMPTOMS & SIGNSmild hemolytic anemia (esp. in premature infants)
spinocerebellar disease (indistinguishable from classic Friedreich ataxia) see Mov50 p.
reproduction disorders (?) see 2733 (15a) p.
LABORATORY DIAGNOSISplasma [tocopherol]↓; varies with total plasma lipid levels, which affect partition between plasma and
adipose tissue, main storage depot for tocopherols (hiperlipidemijos atveju padidėja vitamino E koncentracija)
peroxide hemolysis↑ (enhanced susceptibility of RBCs to hydrogen peroxide).
creatinuria (on creatine-free diet), necrosis in muscle biopsies.
PROPHYLAXIS- preventive dose of α-tocopherol (0.5 mg/kg for full-term infants and 5-10 mg/kg for premature infants).