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ANEMII MEGALOBLASTICE ANEMII MEGALOBLASTICE
33

Curs 2. Anemii Mega Lob Last Ice

Jun 18, 2015

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Page 1: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICEANEMII MEGALOBLASTICE

Page 2: Curs 2. Anemii Mega Lob Last Ice

Frotiu de sange periferic – aspect normal

Page 3: Curs 2. Anemii Mega Lob Last Ice

Celula stem multipotenta: - autoreplicare - migrare in sange periferic - diferentiere ( angajare )

CFU = Unitati Formatoare de Colonii( CS angajate )

Linia mieloida Linia limfoida

Page 4: Curs 2. Anemii Mega Lob Last Ice

rearanjament genic => diferentiereCFU = Unitati Formatoare de

Colonii( CS angajate )

Linia mieloida Linia limfoida

Page 5: Curs 2. Anemii Mega Lob Last Ice

Maturatie: - reducerea dim. nucleare - hemoglobinizarea citoplasmei

Page 6: Curs 2. Anemii Mega Lob Last Ice

Durata: 7-8 zile etapa de reticulocit: - 2 zile in maduva - 1 zi in sangele periferic

Page 7: Curs 2. Anemii Mega Lob Last Ice

Reticulocitele = indicator de erotropoieza

Page 8: Curs 2. Anemii Mega Lob Last Ice

Reticulocite – coloratie supravitala (fara fixare) cu albastru cresyl

Page 9: Curs 2. Anemii Mega Lob Last Ice

Durata de viata a reticulocitelor = 3 zileDurata de viata a reticulocitelor = 3 zile

- 2 zile in maduva- 2 zile in maduva

- 1 zi in sange- 1 zi in sange

Numar de reti. = 0,5 – 1,5 % ( 90 000 / Numar de reti. = 0,5 – 1,5 % ( 90 000 / μl )μl )

TIMPUL DE MATURATIE CORELAT CU HEMATOCRITULTIMPUL DE MATURATIE CORELAT CU HEMATOCRITUL

Hematocrit (%)Hematocrit (%) maturatie ( zile)maturatie ( zile)

4545 11

3535 1,51,5

2525 22

1515 2,52,5

Indice de productie ( Ip) = % Rt x Ht real x 1 Ht ideal timp de maturatie Ip > 3 = An. Hiperregenerativa Ip < 2 = An. Hiporegenerativa

Page 10: Curs 2. Anemii Mega Lob Last Ice

Indice de productie ( Ip) = % Rt x Ht real x 1 Ht ideal 2

Ip > 3 = An. Hiperregenerativa Ip < 2 = An. Hiporegenerativa

Page 11: Curs 2. Anemii Mega Lob Last Ice

ANEMIE – ANEMIE – scaderea cant. de sangescaderea cant. de sange

CLASIFICARE (hemograma):CLASIFICARE (hemograma):

- An. hipocrome microcitare- An. hipocrome microcitare

- An. normocrome normocitare - An. normocrome normocitare

- An. macrocitare - An. macrocitare

Page 12: Curs 2. Anemii Mega Lob Last Ice
Page 13: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICEANEMII MEGALOBLASTICE

Grup de boli a caror tulburare fundamentala este Grup de boli a caror tulburare fundamentala este deficitul sintezei de ADN => afectarea celulelor cu deficitul sintezei de ADN => afectarea celulelor cu rata mare de proliferare: precursori hematopoietici rata mare de proliferare: precursori hematopoietici si celule epiteliale gastro-intestinalesi celule epiteliale gastro-intestinale

Page 14: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICEANEMII MEGALOBLASTICE

Acidul Folic:Acidul Folic: Forma naturala: Forma naturala: acid pteroilmonoglutamicacid pteroilmonoglutamic Sursa alimentara: Sursa alimentara: legume verzi, fructe ( lamai, banane, pepene ), legume verzi, fructe ( lamai, banane, pepene ),

ficat, rinichi, produse lactateficat, rinichi, produse lactate Necesar: Necesar: 400 400 μg / zi, μg / zi, 600 600 μg / zi (gravide ), μg / zi (gravide ), 500 500 μg / zi (alaptare)μg / zi (alaptare) Absortie: Absortie: jejun proximal - forma monoglutamica ( F ) => FH 2 => jejun proximal - forma monoglutamica ( F ) => FH 2 =>

FH4FH4 Transport plasmatic: Transport plasmatic: 6 – 20 6 – 20 μg / μg / ll Depozit: 5Depozit: 5 – 20 m – 20 mg ( pentru 3 luni)g ( pentru 3 luni) Rol: forma activa – Rol: forma activa – tetra hidrofolat ( FH4 ) cu 2 situsuri active N5 tetra hidrofolat ( FH4 ) cu 2 situsuri active N5

si N10 pe care se pot atasa grupari de un atom de carbon ( formil, si N10 pe care se pot atasa grupari de un atom de carbon ( formil, metil, forminino, metinil)metil, forminino, metinil)

N5 – formil FH4 = acid folinicN5 – formil FH4 = acid folinic N5 - metil FH4 = forma de transport si depozit pt FH4N5 - metil FH4 = forma de transport si depozit pt FH4 Rol in sinteza bazelor azotateRol in sinteza bazelor azotate

Page 15: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICEANEMII MEGALOBLASTICE

Cobalamina:Cobalamina: Structura: Structura: - porfirina ( corina)- porfirina ( corina) - atom de cobalt central- atom de cobalt central doua forme active metabolic: - metilcobalaminadoua forme active metabolic: - metilcobalamina - adenosilcobalamina- adenosilcobalamina forma de sinteza - ciancobalamina (vit B12) forma de sinteza - ciancobalamina (vit B12) Sursa alimentara: carneSursa alimentara: carne, ficat, peste, produse lactate, oua, ficat, peste, produse lactate, oua Necesar: 2 - 5Necesar: 2 - 5 μg / ziμg / zi Absortie: Absortie: proteina R – stomacproteina R – stomac factorul intrinsec – duodenfactorul intrinsec – duoden absortie in ileon prin receptori specificiabsortie in ileon prin receptori specifici Transport plasmatic: Transport plasmatic: 200 – 900 n 200 – 900 ng /g /ll 3 proteine specializate ( transcobalamina I, II, III )3 proteine specializate ( transcobalamina I, II, III ) Depozit: 2- 5Depozit: 2- 5 m mg ( pentru 3 – 6 ani )g ( pentru 3 – 6 ani )

Page 16: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICEANEMII MEGALOBLASTICE

Cobalamina:Cobalamina:

Rol: Rol:

AdenosilcobalaminaAdenosilcobalamina: conversia METILMALONIL : conversia METILMALONIL CoA in SUCCINIL COACoA in SUCCINIL COA

glucide / acizi grasi => Acid propionic (mielotoxic) glucide / acizi grasi => Acid propionic (mielotoxic) => propionil CoA => Metilmalonic CoA => propionil CoA => Metilmalonic CoA

MetilcobalaminaMetilcobalamina: conversia HOMOCISTEINEI in : conversia HOMOCISTEINEI in METIONINA METIONINA

reactie de metilare – donator metil FH4reactie de metilare – donator metil FH4

Metionina => adenosilmetionina = > rol in reactiile de Metionina => adenosilmetionina = > rol in reactiile de metilare ( acizi nucleici, histone, fosfolipide, metilare ( acizi nucleici, histone, fosfolipide, neurotransmitatori)neurotransmitatori)

Page 17: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: CauzeANEMII MEGALOBLASTICE: Cauze1. Deficit de folati:1. Deficit de folati: - dieta inadecvata - deficit de absortie - necesar crescut

2. Deficit de cobalamina: 2. Deficit de cobalamina: - - Deficit de absortie - cauza gastrica - cauza intestinala - insuficienta pancreatica - Dieta inadecvata

3. Anemia megaloblastica acuta:3. Anemia megaloblastica acuta: 4. Droguri: 4. Droguri: citostatice, trimethoprim, anticonvulsivante,

contraceptive orale

5. Cauze ereditare: 5. Cauze ereditare: aciduria orotica, sindr. Lesh – Nyhan, A.M cu raspuns la tiamina, anemia diseritropoietica congenitala

6. Anomalii dobandite de etiologie neprecizata:6. Anomalii dobandite de etiologie neprecizata: Anemia megaloblastica refractara, eritroleucemia

Page 18: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: PatogenezaANEMII MEGALOBLASTICE: Patogeneza Deficitul sintezei de AND => asincronism de maturatie

nucleo – citoplasmatic => suferinta sistemelor celulare cu rata mare de proliferare:

-> epiteliu digestiv => tulb. de troficitate

-> tesut hematopoietic => hematopoieza ineficienta

- hiperplazie eritroida medulara

- Indice productie scazut

- turnoverul Fe plasmatic crescut

- scade incorporarea Fe in eritroblasti

- BI / urobilinogen / LDH crescute

deficit de cobalamina = > mielotoxicitate

Page 19: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: Tablou clinicANEMII MEGALOBLASTICE: Tablou clinic

Sindrom anemic

Sindrom digestiv

Sindrom neurologic (in deficit de cobalamina)

Page 20: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Dg. de anemie megaloblastica

Dg. etiologic

Page 21: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Dg. de anemie megaloblastica

HEMOGRAMA: - anemie, uneori pancitopenie

- macro- ovalocitoza oxifila

- pokilocitoza

- indice de productie scazut

- hipersegmentare granulocitara

- VEM > 100 fl;

MEDULOGRAMA

Page 22: Curs 2. Anemii Mega Lob Last Ice

Anemia megaloblastica – frotiu sange periferic

Page 23: Curs 2. Anemii Mega Lob Last Ice

Anemie megaloblastica: frotiu de sange periferic

Page 24: Curs 2. Anemii Mega Lob Last Ice

Anemie megaloblastica: frotiu de sange periferic

Page 25: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Dg. de anemie megaloblastica

MEDULOGRAMA: - hiperplazie eritroida tip megaloblastic = “maduva albastra”

- metamielocite gigante

- megacariocite hiperlobulate

Page 26: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Promegaloblastul (20-30μ) – nucleu voluminos putin excentric, cromatina fin perlata, nucleoli mari

- citoplasma intens bazofila cu zona perinucleara clara

Megaloblast bazofil : - nucleu mai mic, fara nucleoli, cromatina mai densa ( dar nu gramezi)

Megaloblastul policromatofil -nucleu inca mare, cromatina incepe sa formeze blocuri

- citoplasma bogata, policromatofila Megaloblast oxifil (10-18μ) - nucleu cu structura cromatiniana

inca perceptibila - citoplasma oxifila Seria granulocitara - metamielocite gigante, hipersegmentare

granulocitara Seria megacariocitara - talie mare, hiperlobulate

Page 27: Curs 2. Anemii Mega Lob Last Ice

Anemie megaloblastica: maduva

Page 28: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Biochimie: - creste BI / LDH / urobilinogen

- sideremia crescuta

Page 29: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Dg. etiologic:

1. Deficit de cobalamina:

- cobalaminemia sub 100 ng / L

- creste eliminarea urinara de acid metilmalonic

- creste nivelul seric de homocisteina / acid metilmalonic

- testul Schilling

- EDS

- investigatii imunologice

Page 30: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic laboratorANEMII MEGALOBLASTICE: diagnostic laborator

Dg. etiologic:

2. Deficit de folat:

- scaderea folatului seric sub 5 µg / L

- scaderea folatului eritrocitar sub 160 µg / L (eritrocite)

Page 31: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: diagnostic ANEMII MEGALOBLASTICE: diagnostic

Dg etiologic => proba terapeutica Probleme de diagnostic:

- anemii pluricarentiale

- anemii megaloblastice incomplet tratate

Page 32: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: Terapie ANEMII MEGALOBLASTICE: Terapie

1. Deficit de cobalamina:

- terapia etiologica

- terapia de substitutie:

100 – 1000 µg / zi im – 2 saptamani

100 – 1000 µg / sapt. im

100 – 1000 µg / luna im – toata viata ATENTIE: - dinamica raspunsului

- consumul de fier

- urmarirea pe termen lung

Page 33: Curs 2. Anemii Mega Lob Last Ice

ANEMII MEGALOBLASTICE: TerapieANEMII MEGALOBLASTICE: Terapie

1. Deficit de folat:

- terapia etiologica

- terapia de substitutie: doza = 1-5 mg / zi

ATENTIE: - dinamica raspunsului

- dozele terapeutice de acid folic corecteaza anemia prin deficit de cobalamina