Sideroblasts are found in the bone marrow of normal, iron-sufficient subjectsIn their most abnormal form (ie, ring sideroblasts), in which the granules may completely surround the nucleus

VITAMIN B12 DEFICIENCY:Dietary intake and absorptionAnimal products (meat and dairy products) provide the only dietary source of Cbl for humans.minimum daily requirement is listed as 6 to 9 micrograms per dayTotal body stores of Cbl are 2 to 5 milligramsadequate absorption of cobalamin from the diet depends upon five factors:Dietary intakeAcid-pepsin in the stomach to liberate Cbl from binding to proteinsPancreatic proteases to free Cbl from binding to R factorsSecretion of intrinsic factor (IF) by the gastric parietal cells to bind to CblAn intact ileum with functional Cbl-IF receptorsCauses of B12 defiecency:Lack of Intrinsic FactorImpaired Intestinal AbsorptionAbsence of Vitamin B12 Transport ProteinInfestation by fish tape worm (Diphylobothrium latum) causes B12 deficiency

Investigation:Blood film for macrocytosis and hypersegmented neutrophilMeasurement of the serum Cbl and the red blood cell (or serum) folate concentrationsEvaluation of specific metabolic intermediates (eg, methylmalonate and homocysteine) which can accumulate in these deficienciesFor the diagnosis of pernicious anemia, the presence of antibodies to intrinsic factor is a helpful finding. Malabsorption of Cbl, and its correction by the addition of intrinsic factor, can be established through use of the Schilling test, when this test is availableTherapeutic trials of Cbl are warranted when the above testing results are in conflict with the clinical diagnosis.

Treatment:I.M. B-12Folate deficiencyFolate deficiency is treated withfolic acidFolic acidcan partially reverse some of the hematologic abnormalities of Cbl deficiency, although the neurologic manifestations will progressFolic acidcan be continued if the underlying condition cannot be eradicated

Charachterized by:A nemia results when the rate of destruction exceeds the capacity of the marrow to produce RBCs(The bone marrow has the capacity to increase its production of R. Cs. up to 8 times)the stimulation of marrow activity results in increased percentage of reticulocytes in the blood.

Etiologic classification of H. A.

Hemolytic anemias:Clinical manifestation:1. Anemia: 2. Jaundice 3. Dark urine or when it darkens. 4. Various degrees of splenomegaly. 5. Leg ulcers & gall stones are rare complications of some H.A. as S.C.A., thalassemia major & congenital spherocytosis

Hemolytic anemias:Laboratory:

1. Evidences of increased Hb breakdown:-- Hemoglobinemia (raised plasma Hb level especially in intravascular hemolysis) -- Raised serum bilirubin (mainly indirect bilirubin). -- Hemoglobinuria, released Hb haptoglobin. -- Raised urine urobilinogen. -- Hemosiderinuria, 2. Evidences of increased erythropoiesis: -- Reticulocytosis, -- Increased normoblasts in the B. smear -- Bone marrow expansion, may produce, frontal bossing, mongoloid facies, bone pain & increased liability for fracture.

Hemolytic anemias:Laboratory: (cont.)

3. Morphological abnormalities of the R. C.: -- Spherocytes : spherocytosis& acquired H. A. -- Elliptocytosis congenital ovalocytosis & rarely in the other forms of H. A. -- Sickle cells in S. C. A. -- Fragmented RC in HUS -- Target cells, in thalassemia, HbC & S.C.A. -- Siderocytes :after splenectomy. (siderocytes are reticulocytes which contain iron granules, which are confirmed by Prussian blue reaction)4. Evidences of shortened RC survival: 51Cr 5. Evidence of increased hemolysis;Can some times be detected by osmotic fragility test

Hemolytic anemias:(Congenital spherocytosis)

Definition:An A.D. inherited disorder characterized by R.C. stromal protein (spectrin) deficiency which makes the R.Cs. become spherical, rigid & more prone to lyse.

Hemolytic anemias:(Congenital spherocytosis)Clinical picture:Various degrees of anemia, jaundice splenomegaly hyperbilirubinemia (neonatal period)Aplastic crisis Hemolytic crisis is less common (leg ulcer and gall stone)

Hemolytic anemias:(Congenital spherocytosis)INV.Peripheral film shows microspherocytesMCH is normal but MCHC is increased.Increased reticulocyte count (except during aplastic crisis).Increased S. indirect bilirubin.Increased osmotic fragility, which becomes more exaggerated after R. C. incubation for 24 hour.Negative coombs test Hb electrophoresis shows normal Hb A. A , Hereditary spherocytosis. B, Hereditary elliptocytosis.

Hemolytic anemias:(Congenital spherocytosis)Treatment:Splenectomyanemia & the accompanying symptoms. The crisis also disappearsprevents gall stone formation(although spherocytosis & increased osmotic fragility however persist.)blood transfusionfolic acid supplement are essential.

Hemolytic anemias:Hereditary elliptocytois

rare AD, Mild hereditary elliptocytosis produces no symptom s; m ore severe varieties can result in neonatal poikilocytosis (shape variation) and hemolysisI n the rare instances when 2 abnormal alleles are inherited (HPP) severe hemolytic anemiaabnorm alities of - and -spectrin

Hemolytic anemias:Hereditary elliptocytoisAnemia, jaundice &splenomegaly are the main manifestationsReticulocyte count is increasedosmotic fragility test & autohemolysis are normal.Splenectomy cures the symptomatic casePrognosis is good as longevity is not affected

Hemolytic anemias:Other rare R.C. shape defect which may cause H.A.-- Hereditary stomatocytosis; AR or AD in which RC with a slit- like central pallor predominates in the peripheral film.Some patients are symptomatic with anemia, jaundice & splenomegaly.Splenectomy may be beneficial.Hereditary acanthocytosis; an AR rare disorder in which there is marked irregularity of the RC surface. Its seen in a syndrome called a- betalipoprotienemia):Steatorrhoea nervous system degeneration retinitis pigmentosa Symptoms are present since infancy & the condition is fatal during childhood.S. level of cholesterol is low

Hemolytic anemiasRed cell enzyme defects

This is an acquired type of H A which is caused by genetic deficiency of G6PD.is responsible for 2 clinical syndromes, episodic hemolytic anemia,chronic nonspherocytic hemolytic anemia.most com m on m anifestation : neonatal jaundice episodic acute hem olytic anem ia,

Hemolytic anemias: G6PD deficiencyHemolysis in the susceptible patients occurs after the administration of one of the following:Fava beans (ingestion or inhalation of its pollen), (Favism)AspirinSulphonamide as bactrim, & some food coloring agents which also contains sulfa.Furadantin & furazolidoneNalidixic acid (nigram)ParacetamolAntimalarials especially primaquine.Vit.KPhenacetin.Chloramphenicol.Naphthalene.Ciprofloxacin.

Hemolytic anemias: G6PD deficiencyH.A. follows administration of the mentioned agents by 1-3 days jaundice, nausea, vomiting, epigastric pain & dark colored urine (hemoglobinurea).Types of epesodic H.A.:(G6PD A) (chronic hemolysis)G6PD B (G6PD Mediterranean).enz. Activity hemizygous males is

Hemolytic anemias: G6PD deficiencyLaboratory investigations:Rapid drop in Hb & R.C. countsRaised reticulocyte countHemoglobinemia & hemoglobinurea Absent haptoglobin G6PD enzyme activityTreatment:Blood transfusion Sodium bicarbonate;

Hemolytic anemias:

2- Pyrovate kinase deficiency;An A.R. disorder which may present in the neonatal period as jaundice &anemia.During infancy & childhood anemia, jaundice & splenomegaly are present.Osmotic fragility is normal.Reticulocytosis is present, with erythroid hyperplasia in the bone marrow.Diagnosis is confirmed by demonstration of reduced P.K. enzyme activity in the R.C.

Hemolytic anemias:

Treatment: The severity of the disease decreases after childhoodExchange transfusion may be required in neonates.Blood transfusion on needFolic acid supplementSplenectomy