Hematology

Hematology problems relates to deficient or excesses that occur within the elements of the blood or the coagulation factors. Diseases may be: 1. include those affecting mature cells that are produced from precursors or those due to disorders of cell membrane (spherocytosis) Hb synthesis (thalassemia) and of enzymes G-6PD. 2. due to disorders that involve nutrition deficiencies of iron ,vit K, vit. B12, folic acid. 3. due to immune system for example: immune hemolytic anemia, neutropnia, thrombocytopenia, 4. neoplasms leukemia, neuroblastoma 5. drug reactions like anti inflammatory drugs or genetics disorder like Wilson disease or falcony disease. Hematopoiesis begins with the 3 week of gestation with erythropoiesis in yolk sac by 2M gestation hematopoiesis migrates to liver carry out production of platelets, leukocytes, erythrocytes. During 3 trimester the process of hematopoiesis is shifted from the liver to the BM primarily a very low birth weight infants may have a significant hepatic hematopoiesis but small quantity of BM hematopoiesis. During infancy all BM cavities are active and the ratio between hematopoiesis and stromal elements and fat is very high. As the child grows hematopoiesis is take place in central zones of the body vertebra, sternum, ribs, pelvis, as the marrow of extremities and skull are replaced with fat tissue this replacement is gradual and partially reversible process, hemolysis or BM damage may result in marrow repopulating the cavities in which hematopoiesis had already stopped, a children with chronic hemolysis doesnt replace the marrow with fat to the same as extend as normal child for example children with thalassemia and other disorders involving chronic hemolysis may have large head circumference due to erythropoiesis in bones of the skull hepato- splenomegaly in chronic hemolysis may present its an extramedullary hematopoiesis because of extensive atilization of marrow cavities , very young children dont have marrow reserve of older children and adults and more subjected to BM depletion. The hematopoietic cells consist of a small compartment of pluripotent cells that are capable of forming all myeloid elements a large compartment of committed proliferation cells of myeloid and erythroid and another large compartment of post mitotic maturing cells. The BM is the major storage organ of mature neutrophils it contain about 7 times of intravascular pool of neutrophil and 2.5-5 times as many as cells of myeloid line as that of erythroid line,

In addition small number of megakaryocytes, lymphocytes, plasma cells and stromal cells are stored in marrow erythropoiesis is controlled by erythropoietin a hormone made by a juxtaglomerular apparatus of kidney and to a lesser extent by liver as a response to local tissue hypoxia. The control of erythropoiesis by erythropoietin begins at the hepatic hematopoiesis phase in fetal life the normally high Hb in fetus is due to fetal erythropoiesis production in response to decrease O2 saturation in uterus. Erythropoietin hormone is a glycoprotein that stimulate the primitive pluripotent cells to differentiate along the erythroid line the earliest recognized erythroid cells is erythroblast which form light or more daughter cell, the nucleus become pyknotic as the cell mature this highly specialized red blood cells precursors are engaged primarily in production of globin chain glycolytic enzymes and heme and in the turn over of iron which is taken by transferrin receptors and inserted into Hb within the mitochondria during embryonic and fetal life. The globin genes are activated and inactivated in a sequence in which control mechanism remains poorly understood. Embryonic Hb is produced during yolk sac erythropoiesis and are replaced by fetal Hb during hepatic phase during 3 trimester by gamma chain production gradually and replaced by B-chain production HbA shortly after term birth when the expansion of lung results in increase O2 saturation from 65 in uterus to 100% erythropoietin production stops erythropoisis by 6M of age only few delta chain synthesis and very little Hbf is present. RBC of older children and adults 60 days instead of 120 days and is less deformable membrane and have several enzymatic differences from cells of older children. Production of neutrophils precursors is stimulated by a hormone granulocyte, macrophages colony stimulating factor produced by monocytes and lymphocytes in high concentration, thus hormone is capable of activating neutrophils respiratory explosion and increase expression of complement receptors. The production of mature neutrophils take 14 days but production may be more rapid under condition of stress the rapid increase in neutrophils count that occurs with infection is due to release of stored neutrophils from BM. The mitotic pool consists of meyloblasts ,premeyloblasts, myelocytes, the leukocytes primary and secondary made from these precursors and divide among the daughter cells, but only mature neutrophils are fully functional for phagocytes and bacterial killing . Neutrophils migrate from BM circulate for about 6.5 hour and then enter the tissue where they become stage cells and dont circulate ,monocytes migrate into tissue and become macrophages and may live from 1M till 1 year. Megakaryocytes : multinucleated cells from the primitive stem cells and are polyploidy because of nuclear but not cytoplasmic cells.

Division platelets are formed by invagination of their cell membrane which encompasses cytoplasmic granules, mitochondria and glycogen. Platelets circulates 7-10 days and like RBC have no nucleus, lymphocytes are particularly abundant in BM of young children they are significant components of BM these are primarily B-lymphocytes arising in spleen and lymph node but Tlymphocytes are also present .hematologic normal values vary according to age and sex.

Hematologic disorders
Anemia: represent a decrease in Hb level necessary to meet the tissue demand for O2 delivery .it is not a disease but a sign of many disorders and a complication that may disturb other organ function. The quantitative definition of anemia is any value of Hb or HCT to 2 standard deviation below mean value for this age and sex, this value is less straight forward in young children than adults because normal value varies considerably with age, Hb is high in males than females after puberty and at high altitudes than of see levels. Signs: Pale of skin, fatigue, decrease apettite, for example in iron deficiency anemia. Immunohemolysis: this may be extravascular mediated largely by IgG antibodies or intravascular mediated by complement and antibody coated cells. Isoimmunohymolysis: in newborn period may be due to enlarged variety of antigens, for example ,antibody to RH antigen, it is caused by active immunization of mother against fetal antigens that the mother RBC dont express, anti A and anti B hemolysis is due to passive transfer of naturally accruing of antibodies in mother those cells lack A or B antigen, direct antiglubulin test on mother serum and presence of spherocytes and immature RBC precursors confirm this diagnosis as clinical manifestation may presents jaundice. Pancytopenia: decrease in number of all elements of blood ,WBC, RBC, platelets, that suggest BM failure and examination of BM represents low reticulocytes production less than 2%, total drop of erythrocytes, the abnormal form of leukocytes or myeloid elements are less mature than band form and small platelets. Neutropenia: count less than 1500 absolute number per ml3 for children over 1 year, black children normally have lower count. Signs: fever, oral ulceration, lymphadenopathy, bacteremia, agranulocytosis, congenital or drug induced leukemia. Leukocytosis: increase number of leukocytes or neutrophils more than normal value according to age and sex and increase in infection, in bacterial infection neutrophils are produced from BM to increase circulating count, in chronic infection TB abscess, may cause neutrophilia. Polycythemia: irritation, cyanosis, seizures, jaundice for example cyanotic heart disease.

Hemorrhagic disease
Hemostasis is the stop of the bleeding from damaged blood vessels depends on the interaction between the exposed subendothelial collagen of blood vessels the platelets and plasma coagulation factors. Primary hemostasis includes vasoconstriction and adhesion and aggregation of platelets to form 1 hemostatic plaque within 3-7 min. Secondary hemostasis include the platelets induced activation of thrombin by platelet activation. It requires 8-10 min. 3rd stage of coagulation is clot retraction due to partially the retractile platelet protein thrombostenin, the coagulation pathway are initiated by intrinsic mechanism such as the endothelial surface activation of factor 12 which is catalyzed by prekalkanin and by high MW kininogen. The coagulation cascade may be initiated by extrinsic mechanism in which action promoted by release of tissue factors , the activation of coagulation pathway involve the sequential enzyme activation distal inactivation of coagulation protein which activate components that in turn activate the next cascade link. Thrompocytopnea: count below 150000ml3, mucocutanouse bleeding is the major clinical manifestation of thrampocytopnea or disorders of platelets function. Signs: GI hemorrhages, petechia (idiopathic thrompocytopnea)

Coagulopathy: factor 8 deficiency hymophlia Signs: hemarthrosis, mucosal bleeding

Thrombosis: pulmonary embolisim, DVT Anticoagulant, antithrombin deficiency

DIC: the net effect of the consumption of coagulation factors due to intravascular activation of coagulation factor, and subsequent fibrinolysis, the balance between coagulation and fibrinolysis is also a result of consumption of factors used in coagulation. It is always a associated with primary serious illnesses.