محاضره اطفال وصحه

1. Prepared by
Dr: Mojahed Al-shamag
Hematologic
disorders

2. Hematopoiesis
• Hematologic disorders are those that produce either quantitative or
qualitative defects in the cellular elements of the blood or in those
soluble elements related to hemostasis.
• Hematopoietic tissue is derived from the mesenchymal layer of the embryo.
• Earliest evidence of hematopoiesis is seen in the blood islands of the yolk sac at 2-3
weeks of gestation.
• At 5-6 weeks gestation, hematopoiesis starts in the liver. Liver is the chief site of blood
cells production until the 6™fetal month. Liver continues to produce hemic cells until 2
weeks after birth.
• Spleen, lymph nodes, and thymus are also sites of hematopoiesis during fetal tife.
• Bone marrow is the site for hematopoiesis at 4—5 "fetal month. By the 6 month, bone
marrow becomes the chief focus of blood cell production.
• The earliest hemoglobins detected are Gower and Portland. They disappear by the
third month.

3. • HbF (a,y,), the predominant Hb after the 8° gestational weeks, rises to 90% of the total
Hb by the 6" month of gestation. HbF gradually declines to 70% by the end of a term
gestation and continues to fall postnatally to adult levels (<2%) by 12 months of age.
• HbA (a)B2) is the predominant adult hemoglobin. It appears in small amounts very early
in gestation and rises to 30% of the total Hb at term and to 95% by 1 year of age.
• The other adult hemoglobin, HbA, (a.8,), reaches the normal adult level of 2% to 3.4% by
1 year of age.
• At birth, hematopoiesis is present in most of the bones, especially in the bone marrow of
the long bones. With progressive age active marrow gradually reduces from the distal
portions of the skeleton.

4. Anemia
Definition
• Anemia is present when there is a decrease in the level of hemoglobin in
the blood below the reference level for the age and sex of the individual
• Anemia is defined as a state in which hemoglobin concentration or red cell
volume is 2 standard deviation below the mean for that age or sex.
• Anemia is not a disease itself but is a symptom of another disorder.

5. • Alterations in the level of hemoglobin may occur as
a result of changes in the plasma volume.
o A reduction in the plasma volume will lead to
spuriously high hemoglobin (e.g. in dehydration).
o A raised plasma volume produces a spurious
anemia (e.g. in congestive cardiac failure). After a
major bleed, anemia may not be apparent for
several days until the plasma volume returns to
normal.
• Specific signs of different types of anemia may be
present e.g. koilonychias in iron deficiency anemia,
jaundice in hemolyticanemia, and bone deformities
in thalassemia major.
General considerations

6. • To evaluate a patient with anemia a careful history and examination of the patient
is very important.
• A dietary history is important in a case of nutritional anemia.
• Note any family history of anemia or jaundice (thalassemia).
• Note the presence or absence of jaundice(thalassemia, hemolysis, liver disease),
irritability or pica (iron deficiency or lead poisoning).
• Jaundice and/or splenomegaly are present in a case of thalassemia.
• There may be delayed growth and development in chronic diseases.
• Note the signs of high-output congestive cardiac failure.
• Epistaxis or easy bruising may be present in leukemia or aplastic anemia.
• In malabsorption syndromes, there is chronic diarrhea.
• in case of hemolytic anemia, note possible precipitating factors such as viral illness
or the use of medications.

7. Anemia
General features of anemia
Signs (all are non-specific)
Symptoms (all are non-specific)
􀀐Pallor
􀀐Tachycardia (palpitation)
􀀐Hemic murmurs (functional, systolic).
􀀐Heart Failure in severe anemia (with
hemoglobin < 4 gm/dl)
􀀐 Fatigue, headaches and faintness are
all very common
􀀐 Palpitations
􀀐 Breathlessness
􀀐 Angina
􀀐 Intermittent claudication
Classification of anemia
A. Morphologic Classification

8. B. Etiologic Classification
I. Decreased production

9. II. Increased destruction (hemolytic Anemia)
A. Intra corpuscular causes

11. MICROCYTIC ANEMIA
IRON DEFICIENACNY ANEMIA
Iron metabolism
- Daily requirements: 8-15 mg/day
- Most of dietary iron present in ferric state.
- Iron changes to ferrous by combined action of HCL & vitamin C.
- Only 5-10% of dietary iron is absorbed from the duodenum and proximal jejnum
- Absorbed iron is bound to serum transferrin and stored as ferritin to be used in
a. In bone marrow RBCs
b. In cell enzymes e.g. Catalase, peroxidase, mono amine oxidase (MAO).

12. • Iron deficiency anemia is a disorder characterized by iron deficiency resulting in a microcytic,
hypochromic anemia.
• Anemia due to iron deficiency is the most common hematologic disease of infancy and childhood.
• Rapid growth, insufficient dietary intake, and limited absorption of dietary iron combine to place
children at increased risk for iron deficiency.
• Iron is necessary for many biologic processes, including oxygen transport. Most iron in the body is
found in hemoglobin. Iron is necessary for growth and replacement of daily iron losses is supplied
by the diet. Iron is transported in plasma by a specialized transport protein called transferrin. Iron
stores are concentrated in the liver, bone marrow, and spleen in the form of ferritin, from which iron
can be mobilized readily.
• The body of the newborn infant contains 0.3-0.5 g of iron. Adult iron content is 5 g. To approach
adult level, 0.8-1.5 mg of iron must be absorbed each day from the diet. Because less than 10% of
dietary iron is absorbed from the diet, 8-15 mg of iron daily is necessary in nutrition.

13. • As iron stores are depleted further, serum ferritin levels decline. Serum ferritin is an accurate
indicator of tissue iron stores. In iron deficiency, serum ferritin levels are less than 8-12 g/l. As
iron deficiency continues, serum iron decreases to less than 30 g/dl.
• Total Iron Binding Capacity (TIBC) measures the amount of iron that can bind to serum proteins.
As iron stores are depleted, TIBC begins to increase.
• Transferrin saturation provides a measure of the iron available for hemoglobin synthesis.
Hemoglobin synthesis is impaired at saturations of 10-15%.
• Iron is absorbed more efficiently from human milk than from cow’s milk. So, the diets of formula-
fed or cow milk-fed infants should include iron fortified cereals or formula to prevent iron
deficiency. Newborn infant has iron stores for blood formulation for the first 6-9 months of life;
therefore, dietary iron deficiency is uncommon before 9-24 months of age (unless mother
anemic).

14. Etiology
Nutritional
• Mother anemic, repeated pregnancies
• Increased iron demands (preterm, low-birth-weight babies, congenital cyanotic
heart disease)
• Prolonged breastfeeding, cow milk
• Poor weaning (no meat or green vegetables)
• Impaired absorption of iron (malabsorption, celiac disease)
Blood loss
In neonates
• Feto-maternal transfusion.
• Twin-to-twin transfusion
• Obstetric complications such as placental abruption or
placenta previa
• Bleeding from umbilical cord
• Hemorrhagic disease of newborn
• Cow milk protein allergy

15. In children
• Hookworm infestation
• Meckel’s diverticulum
• Peptic ulcer disease
• Rectal polyps
• Inflammatory bowel disease
Clinical findings
• Mild iron deficiency is relatively asymptomatic.
• Infants with iron deficiency anemia usually have history of consumption of large amounts of cow’s milk and carbohydrates
un-supplemented with iron. Blood loss also must be considered.
• In addition to causing anemia, iron deficiency has adverse effects on behavior and cognitive function (apathy, irritability,
poor concentration). These result from alterations of iron-containing enzymes (monoamine oxidase) and cytochromes.
• As it becomes more severe, the infant manifests:
- Irritability
- Anorexia
- Lethargy
- Easy fatigability
- pica(desire to ingest unusual substance)
• Clinical signs of underlying causes(peptic ulcer)

16. • Milk-fed infant is fat, pale, and sallow
• Other findings include:
- Tachycardia
- Systolic murmur
• If the anemia is very severe (Hb<3 gm/dl), there may
be signs of congestive heart failure:
- Gallop rhythm
- Cardiomegaly
- Distended neck veins
- Hepatomegaly
- Rales

17. Diagnosis
• Hemoglobin level iis low.
• The reticulocyte count is normal or minimaily elevated.
• Leukocyte counts are normal.
• RBC morphology shows microcytic hypochromic anemia (erythrocytes
become smaller than normal with decreased hemoglobin content).
Anisocytosis, poikilocytosis may be seen.
• Mean Corpuscular Volume (MCV), Mean Corpuscular Hemogiobin
(MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC), all
are reduced.
• Serum iron level is decreased.
• lron-binding capacity (the transferrin level) is increased, and the
percentage of saturation is low (usually less than 20%).
• Serum ferritin level is decreased (which is a reflection of low iron stores in
bone marrow}.
• Bone marrow examination usually is not indicated, but when performed, it
shows micro-normobiastic hyperplasia of erythroid elements and
decreased or absent stainabie iron.

18. • The differential diagnosis of microcytic, hypochromic anemia is:
o B-thalassemia (normal or increased levels of serum iron and ferritin, normal iron-binding
capacity, elevated HbF and HbA,, hepatosplenomegaly)
o Lead poisoning
o Anemia of chronic inflammation or infection
Differential diagnosis
• Breast feeding should be encouraged.
• Addition of supplemental iron is recommended at 4 month of age in breastfed babies.
• Infants who are not breastfed should receive iron fortified formula for the first year.
• Encourage the ingestion of food richer in iron.
Prevention

19. • Goals of therapy are to return the hemoglobin to physiologic levels.
• lron therapy: Mild to moderate anemia without signs of cardiac compensation can be managed by administration of
iron. Oral iron is given at a dosage of id 3-6 mg/kg/day of elemental iron. Medicinal iron should be administered
between meals to ensure good absorption. After starting iron therapy, there is a rapid subjective improvement in
neurologic function within 12-24 hours. Reticulocytes begin to increase within 48-96 hours (peak at 5-7 days).
Hemoglobin begins to increase within 4—30 days (rate of hemoglobin rise is about 0.1-0.4 g/dL/day). It takes about 1-3
months for repletion of iron stores. So, treatment is continued for a period of 2-3 months after the hemoglobin level has
returned to normal. This allows replenishment of tissue iron stores. Parenteral iron administration is used occasionally
when there is diarrhea or poor compliance. Total dose is calculated as: mg iron = desired rise in Hb (g/dl) x weight (kg)
x 3
• Dietary Counseling should also be given. In infants give iron fortified milk formula. At weaning age, give eggs, meat,
apple juice, and green vegetables.
• Blood transfusion: In severe anemia with signs of cardiac decompensation, packed red blood cells (2-3ml/kg), are
transfused very slowly and repeated in 12— 24 hours if necessary.
• Correct any cause of chronic blood joss.
• Correct underlying disorders i.e. malabsorption.
Management

20. Vitamin BR12R (Cobalamin) Deficiency
• Derived from cobalamin in food (animal sources). Humans cannot synthesize vitamin BR12R.
• cobalamins released by the acidity of the stomach  combine with R proteins and intrinsic factor (IF)
traverse the duodenum pancreatic proteases break down the R proteins  IF-cobalamin absorbed in the
distal ileum  In the plasma, cobalamin binds to transcobalamin II (TC-II)carries to the liver, bone marrow,
and other sites.
• TC-II enters cells by receptor-mediated endocytosis, and cobalamin is converted to active forms
(methylcobalamin and adenosylcobalamin) important DNA synthesis.
• Plasma other two vitamin BR12R-binding proteins, transcobalamin I and III have no specific transport role but are
known to reflect vitamin BR12R tissue stores.
• Almost all vitamin BR12R in plasma is bound to TC-I and TC-III, and thus the measurement of serum BR12R
concentration reflects the storage of this vitamin.
• Older children and adults have sufficient vitamin BR12R stores to last 3-5 yr.
• In young infants born to mothers with low vitamin BR12R stores, clinical signs of cobalamin deficiency become
apparent in the first 6-18 months of life.

21. ETIOLOGY:
• Inadequate dietary intake of vitamin (rare). is not common in kwashiorkor or infantile marasmus. Breast-fed
infants whose mothers are vegans or themselves have pernicious anemia.
• Lack of IF secretion by the stomach. Congenital pernicious anemia is a rare autosomal recessive disorder
due to an inability to secrete gastric IF or secretion of functionally abnormal IF.
• Impaired intestinal absorption of IF-cobalamin. inflammatory diseases such as regional enteritis or neonatal
necrotizing entero-colitis, terminal ileum has been surgically removed.
• Absence of vitamin BR12R transport protein. ranscobalamin II (TC-II) deficiency is a rare cause of megaloblastic
anemia due to decreased utilization of cobalamin.
CLINICAL MANIFESTATIONS:
• weakness, fatigue, failure to thrive, or irritability.
• pallor, glossitis, vomiting, diarrhea, and icterus.
• Neurologic symptoms include paresthesias, sensory deficits, hypotonia, seizures, developmental delay,
developmental regression, and neuropsychiatric changes.
Nelson Last Minute ۸٤

22. LABORATORY FINDINGS:
• The hematologic manifestations of folate and cobalamin deficiency are identical.
• The neutrophils may be large and hypersegmented.
• neutropenia and thrombocytopenia can occur, simulating aplastic anemia or leukemia.
• Serum vitamin BR12R levels are low
• Serum concentrations of methylmalonic acid and homocysteine are elevated.
• Concentrations of serum iron and serum folic acid are normal or elevated.
• Serum LDH activity is markedly increased a reflection of the ineffective erythropoiesis.
• Moderate elevations (2-3 mg/dL) of serum bilirubin levels also may be found.
• Excessive excretion of methylmalonic acid in the urine (normal amount <3.5 mg/24 hr) is a reliable and
sensitive index of vitamin BR12R deficiency.
TREATMENT:
• parenteral administration of vitamin BR12R (1 mg), usually with reticulocytosis in 2-4 days
• If there is evidence of neurologic involvement, 1 mg should be injected intramuscularly daily for at least 2
wk.
• Maintenance therapy is necessary throughout a patient's life; monthly intramuscular administration of 1 mg
of vitamin BR12R is sufficient.
• Oral not used due to uncertain absorption.

23. It is caused by:
• Inadequate dietary intake or ingestion of goat’s milk
• Malabsorption (celiac disease)
• Increased folate requirements (rapid growth, chronic
hemolyticanemia)
• Anticonvulsant medications (e.g. phenytoin, phenobarbitone), and
cytotoxic drugs (e.g. methotrexate)
• Prematurity (low body stores of folate)
Clinical findings
In infants
• Pallor
• Mild jaundice due to ineffective erythropoiesis
• Tongue is smooth and beefy red
• Irritability with poor feeding
Folic acid deficiency

24. • Pallor
• Paresthesias, weakness, or an unsteady gait
• Decreased vibratory sensation and proprioception
In older children
Diagnosis
• Increased Mean Corpuscular Volume (MCV) and Mean Corpuscular
Hemoglobin (MCH).
• Numerous macro-ovalocytes with anisocytosis and poikilocytosis on
peripheral blood film.
• Neutrophils are large with hypersegmented nuciei.
• WBC count and platelet count are normal with mild deficiencies but in
severe cases may be decreased.
• Bone marrow shows erythroid hyperplasia with large erythroid and
myeloid precursors. Nuclear-cytoplasmic dissociation and ineffective
erythropoiesis is seen.
• Serum indirect bilirubin concentration may be slightly raised.
• In vitamin B12deficiency, there is low serum vitamin B12 level. Serum levels
of intermediate metabolites (methylmalonic acid and homocysteine) are
more helpful for diagnosis.
• In folic acid deficiency, red cell folate level is decreased.

25. Treatment
• Folic acid (1-5 mg/day orally for 3-4 weeks) or vitamin B12 (1 mg IM for 2-4 days) is given
according to the cause of the megaloblasticanemia.
• Children at risk for the development of folic acid deficiencies (premature infants and those
with chronic hemolysis) are given folic acid prophylactically.
• Folic acid should not be given in a patient with megaloblasticanemia until a diagnosis of
folate deficiency has been made. Folic acid is contraindicated in vitamin B12 deficiency.
• Blood transfusion is given if necessary.

26. ‫هللا‬ ‫رعاية‬ ‫في‬ ‫دمتم‬