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 G0 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 + 500 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 )
