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Haematopoiesis and Anemia

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1 Haematopoiesis and Anemia
造血与贫血 Department of Pediatrics Soochow University Affiliated Children’s Hospital

2 Main Point-要点 Master clinical manifestation and diagnosis of anemia
Know well etiology and classification of anemia Know well principle of treatment of anemia Understand hematopoiesis trait and blood change in childhood

3 一、Development of the haematopoietic system -造血系统的发育
Three anatomic stages of haematopoiesis prior to birth mesoblastic stage-中胚叶造血期 hepatic stage-肝脏造血期 myeloid stage-骨髓造血期

TABLE 1 GESTATIONAL HEMATOPOIESIS GESTATIONAL AGE PHASE LOCATION 2 weeks - 2 months Mesoblastic Wall of yolk sac 6 weeks - birth Hepatic Liver 2 1/2 month - birth Myeloid Bone Marrow

5 Mesoblastic haematopoiesis -中胚叶造血
Mesoblastic hematopoiesis occurs in extraembryonic structures, principally in the yolk sac wall where small nests of blood cell production can be visualized, and begins between the 10th and 14th days of gestation. These nests are referred to as "blood islands". By 6–8 wk of gestation the liver replaces the yolk sac as the primary site of blood cell production, and by 10–12 wk extraembryonic hematopoiesis has essentially ceased.

6 Hepatic haematopoiesis -肝脏造血
Islands of blood cell development occur within the liver parenchyma from 6 weeks to birth. Although the liver is the dominant site of hematopoiesis for the first half of gestation, blood cell production also occurs at lesser intensity within the spleen.

7 Myeloid haematopoiesis -骨髓造血
Hematopoiesis within bone marrow begins in the clavicle at about 2 1/2 months. Activity continues to rise until myeloid tissue becomes the major site of hematopoiesis in the latter half of gestation. Myeloid hematopoiesis is centered in most bone marrow (red marrow) during intrauterine life. [Fig1. 2]

8 Each hematopoietic organ houses distinct hematopoietic populations
Each hematopoietic organ houses distinct hematopoietic populations. At 18–20 wk of gestation, >85% of the cells in the fetal liver are erythroid and virtually no neutrophils are present .[Fig 3] In contrast, at the same time, <40% of the cells within the bone marrow are erythroid and ≤15% are neutrophils. The subpopulations of leukocytes present in the liver and marrow also differ with gestation.

9 Figure 1 Haematopoiesis before birth

10 Figure 2 Contrast chart of haematomopesis before/after birth

11 Figure 3 Maturation and differential chart of haematopoiesis

12 2、Haematopoiesis after birth
When bone marrow develops, it eventually assumes the task of forming most of the blood cells for the entire organism. However, maturation, activation, and some proliferation of lymphoid cells occurs in secondary lymphoid organs (spleen, thymus, and lymph nodes). In children, hematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum.

13 The red marrow is then very gradually replaced by inactive, fatty, yellow, lymphoid marrow. The latter begins to develop in the shafts of the long bones and continues until, by years, red marrow is present only in the upper ends of the femur and humerus and in the flat bones of the sternum, ribs, cranium, pelvis and vertebrae. However, because of the growth in body and bone size that has occurred during this period, the total amount of active red marrow (approximately g) is nearly identical in the child and the adult.

14 Extramedullary hematopoiesis -髓外造血
In some cases (for instance infections or anemias), the liver, thymus, and spleen may resume their haematopoietic function, if necessary. This is called extramedullary hematopoiesis. It may cause these organs to increase in size substantially. When situation has been improved, these organs will recover to normal size.

15 3.Normal developmental changes in blood cells
1) Erythrocyte and hemoglobin The hemoglobin and erythrocyte are relatively high in the term newborn infant because of the low oxygen tension prevailing and erythropoietin(EPO) increasing in utero. RBC x1012/L, Hb g/L

16 Physiological anemia -生理性贫血
These values subsequently decline, reaching a nadir (the lowest number) at 2-3 months for term infants. It owns self-limiting and gets adult level at the age of twelve. RBC 3.0x1012/L, Hb 100g/L or so

17 2) White blood cells and differentiation
As already mentioned granulocytes is the collective name given to three types of white blood cell. Lymphocytes are produced in bone marrow from primitive precursors, the lymphoblasts and prolymphocytes.

18 Figure 4 Variation trend of WBC

19 Figure 5 Two cross of granulocytes and lymphocytes

20 Platelets Platelets are produced in bone marrow by a process known as thrombopoiesis. It is the same as adult at birth. x109/L

21 Table 2 Normal Hematological values
Hemoglobin MCV White cell Platelets (g/dl) (fL) (x109/L) (x109/L) Cord blood at all ages 3 months 6months to 6 years years Adult

22 Haemoglobins present at different ages
Hb type Chains Timescales Embryonic Hb HbF α2γ2 Predominant haemoglobin at 8 weeks; 90% of Hb at 6 months and 70% at birth. Less than 2% at 1 year of age and thoughout life Adult Hb HbA α2β2 Dectecable early in the fetus and forms % of Hb at 6 months of gestation and 30% at birth HbA2 α2δ2 2-3% during adult life, 1:30 ratio of HbA2 :HbA

23 二、Outline of Anemia-贫血概述
1. Definition of Anemia-定义 Anemia, one of the more common blood syndrome, occurs when the level of healthy Hb/red blood cells (RBCs) in the body becomes too low. This can lead to health problems because RBCs contain hemoglobin, which carries oxygen to the body's tissues. Anemia can cause a variety of complications, including fatigue and stress on bodily organs.

24 Anemia can be caused by many things, but the three main bodily mechanisms that produce it are:
a) inadequate production of RBCs –RBCs生成不足 b) excessive destruction of RBCs –RBCs破坏过多 c) blood loss –失血 Among many other causes, anemia can result from inherited disorders, nutritional problems (such as an iron or vitamin deficiency), infections, some kinds of cancer, or exposure to a drug or toxin.

25 Microcytic anemia Macrocytic anemia (MCV<75fL) (MCV>100fL)
Table 4 Causes of microcytic and macrocytic anemias-大细胞/小细胞性贫血的原因 Microcytic anemia Macrocytic anemia (MCV<75fL) (MCV>100fL) Iron deficiency Folic acid deficiency Thalassaemia syndromes Vitamin B12 deficiency Lead poisoning Orotic aciduria Chronic infections Liver disease Sideroblastic Hypothroidism Pulmonary hemosiderosis Drug-related damage

26 Normocytic anemia-正细胞性贫血 Figure 6 Causes of the normocytic anemias
High reticulocyte levels Low reticulocyte levels Coomb’s test Normal WBC and Decreased WBC Positve Negative platelets: and/or platelets: Membrane defects:spherocytosis Red cell aplasia Aplastic anemia Autoimmune Hemoglobin defects:sickle cell Leukemia Disease Enzyme deficiencies: Hypersplenism glucose 6-phosphate dehydrogenase Infections Red cell fragmentation: Drug hemolytic uraemic syndrome Renal disease Figure 6 Causes of the normocytic anemias

27 2、 Symptoms and Signs-症状和体征
If your child has anemia, the first symptoms might be mild skin paleness and decreased pinkness of the lips and nailbeds. These changes may happen gradually, though, so they can be difficult to notice. Other common signs include: -irritability -fatigue -dizziness, lightheadedness, and a rapid heartbeat

28 If the anemia is caused by excessive destruction of RBCs, symptoms also may include jaundice, a yellowing of the whites of the eyes, an enlarged spleen, and dark tea-colored urine. In infants and preschoolers, iron deficiency anemia can result in developmental delays and behavioral disturbances, such as decreased motor activity and problems with social interaction and attention to tasks. Research indicates that developmental problems may last into and beyond school age if the iron deficiency is not properly treated.

29 3、Diagnosing Anemia -贫血的诊断
In many cases, doctors don't diagnose anemia until they run blood tests as part of a routine physical examination. A complete blood count (CBC) may indicate that there are fewer RBCs or Hb than normal[Table 5]. Other diagnostic tests may include:

30 Table 5 The criterion of anemia
Age Hemoglobin concentration < 28 days < 145 g/L 1~4 months < 90 g/L 4~6 months < 100g/L 6 months~6 years < 110g/L 6~14 years < 120g/L

31 Blood smear examination(血涂片检查): Blood is smeared on a glass slide for microscopic examination of RBCs, which can sometimes indicate the cause of the anemia. Iron tests(铁检测): These include total serum iron and ferritin tests, which can help to determine whether anemia is due to iron deficiency. Hemoglobin electrophoresis(血红蛋白电泳): Used to identify various abnormal hemoglobins in the blood and to diagnose sickle cell anemia, the thalassemias, and other inherited forms of anemia.

32 Bone marrow aspiration and biopsy(骨髓穿刺和活检):
This test can help determine whether cell production is happening normally in the bone marrow. It's the only way to diagnose aplastic anemia definitively and is also used if a disease affecting the bone marrow (such as leukemia) could be causing of the anemia. Reticulocyte count(网织红细胞计数): A measure of young RBCs, this helps to determine if RBC production is at normal levels.

33 Figure 7 Peripheral blood smear of iron deficiency anemia

34 Figure 8 Bone marrow smear of megaloblastic anemia

35 4、Treatment-治疗 1)Treatment for anemia depends on its cause. It's important not to assume that any symptoms your child may be having are due to iron deficiency. Be sure to have your child checked by a doctor. a)If your child has iron deficiency anemia, the doctor may prescribe medication as drops (for infants) or as a liquid or tablet (for older kids), which usually must be taken for as long as 3 months to rebuild the body's store of iron. The doctor also may recommend adding certain iron-rich foods to your child's diet or reducing milk intake.

36 b)If your teenage daughter is anemic and has heavy or irregular menstrual periods, her doctor may prescribe hormonal treatment to help regulate the bleeding. c)Folic acid and vitamin B12 supplements may be prescribed if the anemia is traced to a deficiency of these nutrients, although this is rare in children.

37 d)Anemia caused by an infection will usually improve when the infection passes or is treated. If a certain medication appears to be the cause, your doctor may discontinue it or replace it with something else — unless the benefit of the drug outweighs this side effect. 2)Depending on the cause, treatment for more severe or chronic forms of anemia may include:

38 a)transfusions of normal red blood cells taken from a donor
b)removal of the spleen or treatment with medications to prevent blood cells from being removed from circulation or destroyed too rapidly c)medications to fight infection or stimulate the bone marrow to make more blood cells

39 d)In some cases of sickle cell anemia, thalassemia, and aplastic anemia, bone marrow transplantation may be used. In this procedure, bone marrow cells taken from a donor are injected into the child's vein; they then travel through the bloodstream to the bone marrow and begin producing new blood cells.

40 5、Preventing Anemia -贫血的预防
Whether anemia can be prevented depends on its cause. Currently, there is no way to prevent anemia due to genetic defects affecting the production of RBCs or hemoglobin. However, you can help prevent iron deficiency, the most common form of anemia. Before following any of these suggestions, be sure to talk them over with your doctor:

41 Cow's milk consumption. During the first 6 months of life, babies are usually protected against developing iron deficiency by the stores of iron built up in their bodies before birth. But after month 6, they often don't get enough iron through breast milk alone or regular cow's milk (which contains less iron than fortified infant formula). Regular cow's milk can cause some infants to lose iron from their intestines, and drinking lots of it can make a baby less interested in eating other foods that are better sources of iron.

42 For these reasons, regular cow's milk is not recommended for children until they reach 1 year of age and are eating an iron-rich diet. In addition, they should not drink more than ounces ( ml) of milk each day. If you can't get your child to eat more iron-rich foods, speak with your doctor about giving your child an iron supplement.

43 Iron-fortified cereal and formula.
These products can help ensure that your baby is getting enough iron, especially during the transition from breast milk or formula to solid foods.

44 Well-balanced diet. Make sure that your kids regularly eat foods that contain iron. Good choices include iron-fortified grains and cereals, red meat, egg yolks, leafy green vegetables, yellow vegetables and fruits, potato skins, tomatoes, molasses, and raisins. If your child is a vegetarian, you'll need to make an extra effort to ensure sufficient iron sources because iron found in meat, poultry, and fish is more easily absorbed than iron found in plant-based and iron-fortified foods.

45 Also, be aware that certain food combinations can inhibit or promote absorption of iron. For example, drinking coffee or tea (including iced tea) with a meal can significantly lower the amount of iron absorbed. On the other hand, vitamin C helps the body absorb iron.

46 Summary-小结 Hematopoiesis consists of two phases and three stages.
Physiological anemia and extramedullary hematopoiesis are special phenomena in childhood. Anemia is syndrome,not a kind of specific disease. It is very important for treatment for anemia to seek its causes and find the way to cure. Health education can help prevent iron deficiency, the most common form of anemia.

47 Thank You!

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