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ENDOCRINE SYSTEM, METABOLISM: Vitamins

VitaminsASCORBIC ACID (VITAMIN C).................................................................................................................3

BIOTIN (VITAMIN H)................................................................................................................................5

NIACIN (NICOTINIC ACID, VITAMIN PP).................................................................................................6

PANTOTHENIC ACID.................................................................................................................................8

THIAMINE (VITAMINE B1)........................................................................................................................8

RIBOFLAVIN (VITAMIN B2).....................................................................................................................10

PYRIDOXINE (VITAMIN B6).....................................................................................................................11

RETINOL (VITAMIN A)...........................................................................................................................12

TOCOPHEROL (VITAMIN E)...................................................................................................................14

Cobalamin (VITAMIN B12) → see HEMATOIMMUNOLOGY

Folic acid → see HEMATOIMMUNOLOGY

Vitamin K → see HEMATOIMMUNOLOGY

Cholecalciferol (VITAMIN D3) → see p. 2731 (11-13), 2756, 2754 (9)

VitaminCofactor form:

associated enzymes

Disease caused by deficiency

RDA (sources)

Ascorbic acid

(vit. C)

Ascorbate:

1.Prolyl and lysyl hydroxylases

2.Dopamine -hydroxylase

Scurvy (bleeding gums, perifolliculitis, nonhealing wounds, bones, dentin)

60-90 mg

(citruses, raw vegetables)

Biotin

(vit. H)

Biotin:

four carboxylases

Multiple carboxylase deficiency (seborrheic dermatitis, glossitis, ketoacidosis, retardation)

not established

(30-300 μg)

(intestinal m/o)

Folic acid* Tetrahydrofolate:

enzymes that transfer one-carbon units

Megaloblastic anemia, birth defects

400 g

(green leafy vegetables, liver, yeast)

Niacin (nicotinic acid, vit. PP)

NAD+, NADP+:

dehydrogenases

Pellagra (3D: dermatosis, diarrhea, dementia; glossitis)

16-20 mg

(10 susidaro iš Trp; 90 gaunama su įvairiu

2733 (1)


maistu)

Pantothenic acid Coenzyme A:

various enzymes

nepasitaiko not established (5-10 mg)

(įv. maistas, intestinal m/o)

Thiamine

(vit.B1)

Thiamine pyrophosphate (TPP):

1.-keto acid decarboxylases (carbohydrate metabolism)

2. transketolase

(pentose monophosphate pathway)

Dry beriberi (leg polyneuropathy), wet beriberi (high output cardiac failure), Wernicke-Korsakoff syndrome

1.2-1.5 mg

(įv. maistas)

Riboflavin

(vit.B2)

FMN, FAD:

Oxidoreductases (protein metabolism, etc)

Ariboflavinosis (angular stomatitis, cheilosis, seborrheic dermatitis, corneal neovascularization)

1.3-1.7 mg

(įv. maistas, ypač pieno produktai)

Pyridoxine

(vit.B6)

Pyridoxal phosphate:

1.Enzymes of amino acid metabolism

2.Glycogen phosphorylase

pasitaiko retai (skin and mucosa, convulsions, sideroblastic anemia)

1.7-2 mg

(intestinal m/o, įv. maistas)

Cobalamin (vit.B12)*

5’-Deoxyadenosylcobalamin:

Methylmalonyl CoA mutase

Methylcobalamin:

Homocysteine methyltransferase

Pernicious anemia (megaloblastic anemia + subacute combined degeneration of spinal cord)

2-6 g

(intestinal m/o, visi produktai išskyrus augalinius)

VitaminCofactor form:

primary function

Disease caused by deficiency

RDA (sources)

Retinol

(vit. A)

11-cis retinal:

rhodopsin (vision)

Nyctalopia, xerophthalmia, Bitot’s spots, epithelial hyperkeratosis, reproduction disorders

1000 g (3000 IU) retinol equivalents

(dark green leafy and yellow vegetables, fish liver oil)

Tocopherol

(vit. E)

antioxidant Hemolytic anemia, spinocerebellar disease, reproductive disorders (?)

8-10 mg (15-30 IU)

(vegetables, seed oil)

Vitamin K* various forms of vitamin K:

γ-carboxylation of glutamate residues in blood-clotting enzymes (II, VII, IX, X)

Bleeding 65-120 g

(intestinal m/o, plants)

Cholecalciferol

(vit.D3)

1,25-dihydroxycholecalciferol:

regulation of calcium metabolism

Rickets (children), osteomalacia (adults)

10-20 g cholecalciferol = = 400-800 IU vit. D

(sintezuojamas odoje UV

2733 (2)


poveikyje; fish liver oils, egg yolk, fortified milk)

*see HEMATOIMMUNOLOGY

RDA (Recommended Daily Allowance) (from "MERCK Manual", 17 ed., 1999): see also 2732 (5) p.

2733 (3)


ASCORBIC ACID (VITAMIN C)

RDA60 mg (pregnancy - 70 mg, lactation - 95 mg)

SOURCES1. Citrus fruits, tomatoes, broccoli, cabbage

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:

2733 (4)


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+).

4. Antioxidant – protects against free radicals.

5. Protects folic acid reductase (folic acid → folinic acid).

SCURVY (s. SCORBUTUS)

ETIOLOGY1. Food idiosyncrasies or improper diet (e.g. "ulcer diet" - achlorhydria decreases amount absorbed)

< 10 mg/d.

2. Heat (e.g. sterilization of formulas, cooking) can destroy vitamin C in food.

3. Pregnancy, lactation, inflammatory diseases, surgery, burns, thyrotoxicosis - increased demands.

4. Diarrhea - increased fecal loss.

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.

2733 (5)


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).

2733 (6)


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)


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.

2733 (8)


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):

1. Pyruvate carboxylase (pirmoji gliukoneogenezės reakcija: pyruvate → oxaloacetate)

2. Acetyl CoA carboxylase (pirmoji fatty acid synthesis reakcija: acetylCoA → malonylCoA)

3. Propionyl CoA carboxylase (fatty acids su nelyginiu C atomų skaičiumi oksidacija)

4. -Methylcrotonyl CoA carboxylase

DEFICIENCY & DEPENDENCY

ETIOLOGYDeficiency:

1. Antibiotikoterapija

2. Nevirtų kiaušinių vartojimas (raw egg white contains AVIDIN – has very high affinity to biotin – prevents absorption).

Dependency – genetic defects of:

Biotin holocarboxylase synthetase

Biotinidase

SYMPTOMS & SIGNS- MULTIPLE CARBOXYLASE DEFICIENCY: see 2733 (5a) p.

Deficiency:

1. Seborrheic dermatitis, hair loss (vit. H – vok. Haut – oda)

2733 (9)


2. Anorexia and glossitis

3. Ketoacidosis

4. Muscular pain

Dependency:

1. Developmental retardation

2. Defects in T-cell and B-cell immunity

LABORATORY DIAGNOSISUrinary excretion of various organic acids – karboksilazių nepanaudoti (arba metabolizuoti alternatyviais keliais) substratai.

TREATMENTDeficiency – biotin 150-300 μg/d.

Dependency – large doses of biotin (5-50 mg/d).

NIACIN (NICOTINIC ACID, VITAMIN PP)- part of vitamin B complex.

Therapeutic uses:

1) pellagra (vit. PP – pellagra-preventing)

2) vasodilator

3) hyperlipidemia (cholesterol-lowering and HDL-raising agent) see 780 p. (in BIOCHEMISTRY)

RDA- up to 20 mg.

1 niacin equivalent = 1 mg niacin = 60 mg dietary Trp

SOURCES10% susidaro organizme iš Trp.

2733 (10)


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)

malignant carcinoid tumor (Trp sunaudojamas serotonino gamybai)

Hartnup disease (sutrikusi Trp absorbcija žarnyne ir reabsorpcija inkstuose)

diarrheas, cirrhosis, alcoholism, etc

SYMPTOMS & SIGNSDermatosis + diarrhea + dementia (+ death) see 2733 (6a) p.

1. Cutaneous lesions ( dermatosis ) - acute photosensitive rash: sunlight causes CASAL necklace and butterfly-shaped lesions on face.

galimi ir kitokie odos pažeidimai.

distribution of lesions (at trauma points, usually bilaterally symmetric) is more characteristic than their form.

secondary infections are common.

2. Mucous membrane symptoms - scarlet glossitis and stomatitis; ulcerations may appear.

3. GI symptoms - serious diarrhea, often bloody because of GI hyperemia and ulceration.2733 (11)


4. Neuro symptoms : (1) encephalopathic syndrome (cognitive deficits*, personality changes that progress to delirium), (2) peripheral neuropathy.

differentiating neuro symptoms from those in thiamine deficiency is difficult.

*irreversible dementia can result if deficiency is not treated

LABORATORY DIAGNOSISUrinary excretion of N´-methylnicotinamide (NMN) is decreased (< 0.8 mg/d suggests niacin deficiency).

TREATMENTNiacinamide* 300-1000 mg/d orally.

*niacin can cause flushing, itching, burning, tingling.

Multiple deficiencies of B vitamins and protein often occur together - other B-complex vitamins should also be given in therapeutic dosages.

e.g. neuropathy does not improve with niacin supplements; symptoms improve only when thiamine and pyridoxine are added.

PANTOTHENIC ACID- part of vitamin B complex.

RDA- not established (4-7 mg – safe & adequate)

SOURCES- widely distributed in various foods + sintezuoja žarnyno flora.

METABOLISM & FUNCTIONS- precursor of coenzyme A (acyltransfer cofactor).

2733 (12)


DEFICIENCY is rare in humans.

THIAMINE (VITAMINE B1)

RDA1-1.5 mg (0.5 mg/1000 kcal)

SOURCES- įvairus maistas; kepenyse atsargos nedidelės (≈ 2 savaitėms).

total body store is 30-100 mg (in heart, skeletal muscle, liver, kidneys, brain).

METABOLISM & FUNCTIONSATP pagalba iš thiamine susidaro aktyvi forma thiamine pyrophosphate (TPP) - coenzyme for:

1) α-KETO ACID DECARBOXYLASES (carbohydrate metabolism) t.y. pyruvate dehydrogenase (decarboxylase) – smulkiau žr. 704 p. (in BIOCHEMISTRY)

2) TRANSKETOLASE (pentose monophosphate pathway) – smulkiau žr. 693 p. (in BIOCHEMISTRY)

BERIBERI

(Singhalese word beri – weakness)

ETIOLOGY

Primary deficiency - inadequate thiamine intake (esp. in people subsisting on highly polished rice).

Secondary deficiency is caused by:

increased requirement (hyperthyroidism, pregnancy, lactation, fever).

impaired absorption (prolonged diarrheas, hyperemesis gravidarum).

impaired utilization (severe liver disease).

2733 (13)


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↓

2733 (14)


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).

RIBOFLAVIN (VITAMIN B2)

RDA1.2-1.5 mg (iki 1.7 mg)

SOURCES- įvairus maistas, ypač pieno produktai.

METABOLISM & FUNCTIONSintestinal mucosa: riboflavin → FMN

2733 (15)


liver: FMN → FAD

FMN ir FAD yra OKSIDOREDUKTAZIŲ koenzimai (protein metabolism, etc).

see 680 p. (in BIOCHEMISTRY)

ARIBOFLAVINOSIS

ETIOLOGYn.y. (greičiau susergama, jei vartojama mažai baltymų)

SYMPTOMS & SIGNS1. Mucosal fissuring - pallor and maceration of mucosa in mouth angles (angular stomatitis) and

vermilion surfaces of lips (cheilosis) → superficial linear fissures → leave scars when healed.

N.B. gerokai dažnesnė angular stomatitis priežastis yra žemi protezai (ar iš viso jų nedėvėjimas) – lūpų kampai įsiverčia į vidų ir maceruojasi.

2. Seborrheic dermatitis (paraudimai aplink angas - genitalia, face).

3. Rarely, corneal neovascularization and epithelial keratitis.

see 2733 (10a) p.

LABORATORY DIAGNOSISUrinary riboflavin↓

Increased activation of RBC glutathione reductase by riboflavin - early sign of deficiency.

Klinika nespecifinė, todėl reikia remtis:

laboratory tests

elimination of other causes

therapeutic trial

2733 (16)


TREATMENTRiboflavin 10-30 mg/d until response is evident (minimum 2 sav.)

PYRIDOXINE (VITAMIN B6)

RDA1.7-2 mg

SOURCES- įvairus maistas; gausiausiai žarnyno floros sintezuojamas vitaminas!

METABOLISM & FUNCTIONS vitamin B6 comprises group of closely related compounds: PYRIDOXINE, PYRIDOXAL, and

PYRIDOXAMINE.

they are phosphorylated to PYRIDOXAL PHOSPHATE – cofactor for:

A. Nitrogen metabolism - enzymes that use amino acids as substrate (pyridoxal phosphate prijungia amino acid prie enzimo):

transaminations

deaminations

decarboxylations

racemizations

aldol cleavages

various reactions at β and γ carbons

(pvz. niacino susidarymas iš Trp, hemo sintezė)

B. GLYCOGEN PHOSPHORYLASE (glycogen metabolism)

DEFICIENCY2733 (17)


ETIOLOGY PRIMARY DEFICIENCY – rare (most foods contain vitamin B6).

SECONDARY DEFICIENCY - chemical inactivation by drugs (e.g. isoniazid, penicillamine).

autosomal recessive DEPENDENCY STATES - vit.B6 apoenzimų mutacijos.

SYMPTOMS & SIGNS1. Skin and mucosa – seborrheic dermatosis, glossitis, etc.

2. CNS – generalized clonic seizures (ypač kūdikiams, maitinamiems rafinuotais mišinukais); in dependency states, seizures can occur in utero!

pyridoxine is essential for synthesis of glutamic acid decarboxylase (enzyme for synthesis of GABA).

untreated pyridoxine dependency → persistent seizures, uniform severe mental retardation.

3. Peripheral neuropathy (axon loss, sensory > motor).

4. Sideroblastic anemia (pyridoxal phosphate is needed in formation of δ-aminolevulinic acid, rate-limiting step in heme biosynthesis).

LABORATORY DIAGNOSIS- whole blood [pyridoxal phosphate]↓

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.

2733 (18)


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

2733 (19)


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)


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

2733 (21)


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!

2733 (22)


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

2733 (23)


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).

2733 (24)


TREATMENT malabsorption – oral α-tocopherol 15-25 mg/kg/d as water-miscible d-α-tocopheryl acetate (1 mg

= 1.4 IU).

much larger doses are required to treat neuropathy or to overcome defects of absorption and transport.

VITAMIN E TOXICITY

adults have taken large vitamin E amounts (up to 800 mg/d) for years without any apparent harm.

most significant toxic effect of vitamin E at > 1000 mg/day is antagonism to vitamin K leading to hemorrhage.

Panaudota literatūra:

R.BERKOW "MERCK Manual", 17 ed., 1999: 4-11, 33-51 p.

NMS Pathology 1993, NMS Biochemistry 1999

SĄS Nr. 17 “Biochemija 1”

2733 (25)

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