Hematopoiesis from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more.

Sites of Haemopoiesis Yolk sac Liver and spleen Bone marrow Gradual replacement of active (red) marrow by inactive (fatty) tissue Expansion can occur during increased need for cell production

. (Haemopoiesis schematic representation)

Stem cells Self-renewal Normally in G 0 phase of cell cycle The capacity for self-reproduction is vastly in excess of that required to maintain cell production for normal lifetime As cells increase in number they differentiate as well Multipotentialitylineages Capacity to generate cells of all the lymphohaemopoietic

Anaemia Definition Reduction of Hb below normal conc. i.e. < 13 g. / dl for males (P.C.V. < 0.40 L/L) <12 g. /dl for females (P.C.V. < 0.37 L/L)

Types of anaemia (1) Excessive loss or destruction of red cells (a) loss – post haemorrhagic anaemia (b) destruction – haemolytic anaemias (2) Failure of production of red cells (a) diminished production with marrow hyperplasia – dyserythropoietic anaemias e.g. iron deficiency anaemia & megaloblastic anaemia (b) diminished production with marrow hypoplasia --- hypoplastic or aplastic anaemias

Morphological classification I Hypochromic microcytic anaemia A-iron deficiency anaemia B-B -Thalassaemia C-Sideroblastic anaemia II Normochromic macrocytic anaemia (Megaloblastic anaemia) III Normochromic normocytic anaemia A-acute blood loss anaemia B-all haemolytic anaemias except Thalassaemia C-secondary anaemias.. Leukaemia, malignancies in general, collagen and autoimmune diseases, uraemia, chronic liver diseases

Iron Deficiency (ID) A reduced iron supply to the erythron can be absolute due to reduced body iron leading to IDA or functional due to defective iron utilization such as anaemia associated with chronic illnesses.

Causes of IDA Dietary deficiency of Iron (important only when associated with other causes) may arise due to poverty, religious trends and among vegetarians. Malabsorption of iron : this occurs in gluten enteropathy and after gastrectomy. Increased demands: Infancy aggravated by prematurity, infections and delayed mixed feeding. Adolescence Pregnancy : fetal requirements is around 300 mg mg needed for maternal circulation expansion. Blood loss: this is the most important cause of IDA, in females it is most commonly from the genital tract while in males from GIT usually.

Stages of ID ( Sequence of events) Stage of store depletion: Mobilization of storage iron which become depleted by the end of this stage. Increased intestinal iron absorption. Reduced S.ferritin level & disappearance of stainable marrow iron. Red cell indices, red cell morphology and serum iron parameters are all normal.

Stage of Iron deficient erythropoiesis Reduction of transferrin saturation. Increase level of transferrin receptors in the serum. Red cells may show a tendency toward microcytosis. Red cell indices are within normal but tend to rise uppon iron therapy.

Stage of iron deficiency anaemia Reduction in all red cell indices ( Hb, PCV, MCV, MCH & MCHC ) Frank hypochromia and microcytosis. In chronic and severe cases tissue changes develop: Spooning of the nails, stomatits and glossitis. Pharyngeal webs. Pica Villous atrophy Reduced cell mediated immunity Impairment of mental development in children.

Haematological features: Peripheral blood: Hypochromia + microcytosis with mild to moderate anisopoikilocytosis Platelets are usually increased but may be normal, WBCs are normal though few hyper segmented neutrophils may be seen.

Bone marrow BM is usually hypercellular Normoblastic erythroid hyperplasia, normoblasts show shaggy outlines and vacuolated cytoplasm with pyknotic nuclei. Other haematopoietic cells are normal. Absent marrow iron both in erythroid cells and macrophages.

Diagnosis of IDA In most cases: Clinical data. Typical red cell morphology Reduced transferrin saturation In more complicated cases: S. Ferritin B.M iron assessment

Iron overload Excessive body iron may result from: Excessive absorption ( parenchymal iron deposition ) Parentral iron input ( RE deposition mainly )