لو أنا عندي macrocytosis يعني

 macrocytosis 

لو أنا عندي macrocytosis يعني 

MCV more than 96 fl. 

كده ممكن يكون كرات الدم دي كبيرة والسبب في BM 

وتسمي

megaloblastic anemia 

وممكن يكون السبب من خارج ال BM وفي الحالة دي تبقي

non-megaloblastic anemia. 

 نبدأ بال 

non-megaloblastic anemia

 أسبابها :

الRBCs  اللي بتكون في ال

peripheral blood 

كبيرة، بس أبص على ال BM ألاقيه طبيعي ....يبقا دي

Non-megaloblastic macrocytic anemia 

أمثلة ذلك 

1_  hypothyroidism  

2_  Alcohol excess 

3_ Chronic liver disease

 يقولك الامراض دي كلها مش عارفين ازاي؟؟؟ مش هنخش في تفاصيل بتلاقي كرات الدم الحمراء عليها Lipid  على سطحها  عمال يترمي عليها دهون   .... فتلاقي الRBCs  بقت كبيرة كده فتقول دي macrocyte  تيجي تدور على ال

B12  or folic acid deficiency

او تشوف ال BM  مفيش حاجة يبقا دي

macrocytic non-megaloblastic.

ممكن كمان 

5_ hemolytic crisis   due to reticulocytosis 

فتبان كرات الدم كبيرة 

6_ haemagglutination  

ممكن يوصل ال MCV لأرقام عالية 

وفي الحالة دي ال BM مفهوش megaloblast 

7_ Others as pregnancy, neonatal period, cytotoxic drugs, paraproteins. 

         

  megaloblastic macrocytosis 

دي بقي مثل 

Vit B12 and folic acid deficiency 

وأسباب أخر مثل

1_ Hydroxyurea and other

    chemotherapy that interferes with

    DNA synthesis and may increase

    MCV. 

2_ myelodysplastic syndrome 

3_ AML especially M6 

4_ Other hereditary diseases as

     Lesch Nihan syndrome,... etc. 

5_ orotic aciduria and Fanconi anemia 

         __________________________

نتكلم شوية عن أهم الأسباب هي 

VIT B12 causes :

1_  intrinsic factor due to atrophic gastritis. 

2_ chronic gastritis due to either Ab or Helicobacter pyloric or terminal ileum disease. 

3_ pathology of terminal ileum as enteritis

4_ bacterial utilization of serum Vit B12 

Schilling test  differentiates between them. 

5_ other rare causes e.g. drugs as colchicine, neomycin, Metformin,.... 

transcobalamin deficiency, HIV infections, parasitic infestation as diphyllobothrium latum,.... 

6_ #pernicious anemia:

دي B12 deficiency  نتيجة 

autoimmune disease affect stomach leads to lacks of intrinsic factor 

عشان كده فيه حاجة اسمها

anti parietal cell antibody   

وكمان 

anti intrinsic factor antibody  

هو ده الموجود وده مهم جدا جدا جدا المرض ده ساعات بيكون معاه 

associated with another autoimmune disease as myxoedema, thyroiditis, vitiligo. 

لكن  VIT B12 مش ممكن يكون سببه

  intake or  demand

 لأن مخزونه في الجسم كبير. 

Pernicious anemia :

is considered to be an autoimmune disease, in which the body's own immune system mistakenly damages its own tissues. 

It is believed that the decreased absorption of vitamin B-12 from the gastrointestinal tract in pernicious anemia results from the presence of an autoantibody against intrinsic factor (IF), a protein made in the stomach that is necessary for the absorption of vitamin B-12. 

ما هو ال IF? 

intrinsic factor (IF), a protein made in the stomach that is necessary for the absorption of vitamin B-12. 

ما هي فائدته 

Normally, vitamin B-12 binds to intrinsic factor in the stomach, and this facilitates its absorption by the small intestine further along in the digestive process. Along with the autoimmune process that attacks the IF protein and lowers IF levels in stomach secretions, another autoimmune reaction against the stomach lining cells also occurs, resulting in a form of inflammation known as chronic atrophic gastritis.

Pernicious anemia is sometimes associated with other autoimmune diseases such as Graves' disease, vitiligo Hashimoto's thyroiditis, and  (blanching or depigmentation of skin areas).

      

Folic acid deficiency causes :

1_   intake or  demand as in child,

    pregnancy, hemolytic anemia

    Myeloproliferative disorders and

    malignancy. 

2_ intestinal disease 

3_ antifolate drugs as phenytoin, methotrexate, trimethoprim, purine, and pyrimidine analogs. 

4_ alcoholism 

        

Symptoms of megaloblastic anemia:

1_ Megaloblastic macrocytic anemia 

2_ psychiatric abnormalities and visual disturbance 

3_ Vit B12 neuropathy especially in legs, 

4_ neural tube defect may occur in folate and Vit B12 deficiency 

4_ gonadal dysfunction may occur in folate and Vit B12 deficiency but reversible with the appropriate vitamin supplement 

5_ Epithelial cell changes as glossitis and GIT manifestation may occur. 

6_ Cardiovascular disease due to high Homocysteine 

        

Diagnosis of VIT B12 and folic acid deficiency :

1_ sign and symptoms of anemia and GIT manifestations as dyspepsia and glossitis. 

2_ neurological manifestation in VIT B12 deficiency. 

3_ macrocytosis(or macrovalocyte)

4_ blood film   hypersegmented neutrophils anisopokilocytosis, basophilic stippling. 

5_ hyperbilirubinemia (usually indirect) due to Intramedullary hemolysis. 

6_ pancytopenia. 

7_  VIT B12 or folic acid in the blood.

8_ high level of uric acids and LDH due to Intramedullary hemolysis due to ineffective hematopoiesis ( retic). 

9_ High level of Homocysteine,    methylmalonate  in VIT B12 deficiency  

10_ B.M.  hyperplasia of all series (مهم) DD is M6 and Myelodysplasia. 

11_   reticulocytosis in response to B12 and folate therapy. 

بعد ٦ الي ٧ أيام 

        

Serum B12 (cobalamine) ( N: 160_760 nano g/L ) 

ملحوظة مش كل اللي عندهم نقص فيتامين ب ١٢ يبقى عندهم

Megaloblastic anemia 

Mild degrees of B12 deficiency shown by a low serum B12 without macrocytosis are more frequent. 

Serum B12 It has 95 % sensitive but about 50% specific. i.e other causes may decrease Serum B12

ممكن يقاس 

Holotranscobalamin II ( holoTCII) 

الأفضل يقاس 

High level of Homocysteine,    methylmalonate.

في حالات نقص ال cobalamine بيبقي الفوليك أسيد زايد في الدم. 

        __________________________

Other causes that   serum VIT B12 ( no megaloblastic anemia) 

1_ Idiopathic 

2_ pregnancy 

3_ Transcobalamine I ( TCI ) deficiency 

4_ folate deficiency 

5_ multiple sclerosis, aplastic anemia 

6_ PNH 

Causes that   cobalamine (Vit B12) 

مهمة 

1_ CML, AML 

2_ CRF 

3_ cobalamine therapy 

4_ metastatic cancer 

5_ autoantibody to TCII 

Serum folate ( N: 3_20 mic g / L) 

Red cell folate may be measured

 Homocysteine 

Positive FIGLU test  

         _________________________

Treatment: 

Replacement of Vit B12 and folic acid. 

قبل ما تعطي الفوليك اسيد تأكد من عدم وجود 

Cobalamine deficiency 

لأن لو فيه 

Cobalamine deficiency 

وانت اديت folate 

You will improve anemia but you will aggravate neurological manifestation 

Response to treatment ( Vit B12, folate) :

1_ dramatic relief of symptoms 

2_ dramatic reticulocytosis by 2nd to 3rd day and reach maximum at 5th to 8th day 

3_ Hb level increased after 1 week and reach normal in 4_8 weeks 

4_ BM converts from megaloblastic to normoblastic through 2 days 

5_ recovery of CNS may take 6 months 

6_ Homocysteine and methylmalonate begins to fall within a few days of therapy 

6_ monitoring Vit level is within a low value 

Prophylactic folic acid supplementation is indicated in :

1_ pregnancy to avoid NTD 

2_ premature 

3_ chronic hemolytic anemia 

4_ patient in long term hemodialysis