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
