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ERYTHROPOIESIS
CLASSIFICATION OF ANEMIA
&
IRON DEFICIENCY ANEMIA
Dr. Sookun Rajeev K
(MD)
Dept of General Medicine
Anna Medical College
ERYTHROPOIESIS
ERYTHROPOIESIS
•It is the process by which progenitor cells
in the marrow proliferate, differentiate into
Normoblasts and mature into anucleated
reticulocytes which enter the circulation.
•Normal life span of RBC 110-120 days
ERYTHROPOIESIS (cont)
Hematinics necessary for Red Cell formation:
1. Aminoacids for synthesis of chains of
globin
2. Iron for Hb synthesis
3. Vitamin B12 and folic acid for nucleic acid
synthesis of erythroid precursors
4. Zinc
5. Vitamin C to raise absorption of iron from
ferric to ferrous state
ERYTHROPOIESIS (cont)
6. Vitamin E for maintainance of integrity of
red cells
7. Copper helps transfer of iron cells to plasma
with aid of ceruloplasmin
8. Thyroxine
9. Androgen
10.Cobalt trace element as part of vit B12
ERYTHROPOIESIS (cont)
Process of Erythropoiesis
Erythropoiesis is regulated by erythropoietin,
vitamin B12, Folic Acid and Iron
NORMAL HEMOGLOBIN VALUES
AGE HEMOGLOBIN
1 - 3 days 14.5 – 22.5g/dl
6 mo - 2 yrs 10.5 – 13.5 g/dl
12 yrs – 18 yrs male 13.0 – 16.0 g/dl
12 yrs – 18 yrs female 12.0 – 16.0 g/dl
> 18 yrs male 13.5 – 17.5 g/dl
>18 yrs female 12.0 – 16.0 g/dl
ANEMIA
Definition:
Anemia is defined as a reduction in Hct or Hb
concentration.
<13.5 g/dl in adult males
<12.0 g/dl in adult females
<11.0 g/dl in pregnant women
<10.5 g/dl in infants 6 mn to 2 yrs
<11.5 g/dl in children 2 yrs to 12 yrs
ANEMIA (cont)
• When red cell mass (as measured by Hb or less
precisely by Hct) decreases, several compensatory
mechanisms maintain oxygen delivery to the
tissues. These mechanisms include:
Increased cardiac output (heart rate and stroke volume)
Increased extraction ratio
Rightward shift of the oxyhemoglobin curve (increased
2,3-diphosphoglycerate [2,3-DPG])
Expansion of plasma volume
ANEMIA (cont)
• If anemia develops rapidly, symptoms are more
likely to be present, because there is little time for
compensatory mechanisms. When onset is gradual,
compensatory mechanisms are able to maintain
oxygen delivery, and symptoms may be minimal or
absent.
CLASSIFICATION OF ANEMIA
1. Microcytic Anemias (MCV <80 fl)
• Anemia of chronic disease :Decreased iron and decreased TIBC;
increased ferritin
• Sideroblastic anemia: Increased iron and normal TIBC; increased
ferritin. Peripheral smear shows basophilic stippling and ringed
sideroblasts.
• Iron deficiency anemia Decreased iron and increased TIBC.
Ferritin<12 µg/L is very suggestive of iron deficiency.
• Thalassemia Very low MCV (usually <70 fL); normal iron studies.
The peripheral smear may reveal basophilic stippling. Hemoglobin
electrophoresis is needed for diagnosis.
CLASSIFICATION OF ANEMIA
2. Normocytic Anemias (MCV >80 fl,MCV <100 fl)
•Hemorrhage Look for source of blood loss, perform a
Hemoccult's stool
•Glucose-6-phosphate deficiency
•Autoimmune hemolytic anemia Positive Coombs
•Membranopathies Hereditary spherocytosis with
splenomegaly on physical examination
CLASSIFICATION OF ANEMIA
3. Macrocytic Anemias (MCV >100 fl)
•Vitamin B12 or folate deficiency Low serum vitamin
B12 and folate levels. The peripheral smear reveals
hypersegmented neutrophils. Vitamin B12 deficiency
may also have neurologic findings.
•Liver disease Elevated liver function tests, aspartate
aminotransferase, and alanine aminotransferase. The
peripheral smear may reveal target and spur cells.
CLASSIFICATION OF ANEMIA
~400 types of Anemia
Iron Deficiency Anemia
Myeloblastic Anemia
Pernicious Anemia
Hemorrhagic Anemia
Hemolytic Anemia
Thalassemia
Aplastic Anemia
CAUSES OF IRON DEFICIENCY ANEMIA
Iron deficiency results in a defective synthesis of
hemoglobin and smaller red cells (microcytic) with less
hemoglobin within the cell (hypochromic).
In Children
Increased requirements
Inadequate dietary iron
Malnutrition
Low iron stores
Eating disorders
Pica
Lead poisoning.
CAUSES OF IRON DEFICIENCY ANEMIA
In Adults
Gastrointestinal (GI) blood loss are the use of nonsteroidal
anti-inflammatory drugs,
Peptic ulcer disease
Angiodysplasia
Diverticulosis
Malignancy
Rarely, parasites such as Hookworms.
Frequent blood donations and phlebotomies, surgical
procedures
CAUSES OF IRON DEFICIENCY ANEMIA
In Females,
Menstrual disorders,
Pregnancy
Lactation
• The daily loss of iron in an adult is about 1 mg, and
menstrual loss can be an additional 20 mg per
month.
• Normally less than 10% of the daily dietary intake of
iron is absorbed.
HISTORY FROM PATIENT
A.The evaluation should determine if the anemia is
of acute or chronic onset, and clues to any
underlying systemic process should be sought.
B. A history of drug exposure, blood loss, or a
family history of anemia should be sought.
C.Lymphadenopathy, hepatic or splenic
enlargement, jaundice, bone tenderness,
neurologic symptoms or blood in the feces should
be sought.
SIGNS
Tachycardia
Systolic murmur
Dry skin
Dysphagia from pharyngeal and esophageal webs
may also be present.
SIGNS
Pallor of the conjunctiva, lips, nail beds
SIGNS
Palmar skin creases
SIGNS
Nail changes such as brittle and spoon-shaped nails
(koilonychia).
SIGNS
Angular stomatitis,
SIGNS
Glossitis
SYMPTOMS
Weakness
Malaise
Fatigue
Dyspnea on exertion
Palpitations
Dizziness
Chest pain
Headaches
SYMPTOMS
Pica
DIAGNOSIS
1. The test result would depend on the stage of development of iron
deficiency.
2. The classic hypochromic microcytic picture develops when iron
stores are exhausted.
3. Anisocytosis, poikilocytosis, and target cells may be present on
the peripheral smear.
4. Increased red cell distribution width with a low mean corpuscular
volume is suggestive of iron deficiency anemia.
DIAGNOSIS (cont)
1. Full Blood Count
Hemoglobin level
The MCV is normal in early iron deficiency. As the
hematocrit falls below 30%, hypochromic microcytic
cells appear, followed by a decrease in the MCV.
DIAGNOSIS (cont)
2. Peripheral Blood Smear
3. Reticulocyte count
4. Urine Micros
5. Stool for FOB
6. Stool for Ova, Cysts & Parasite
DIAGNOSIS (cont)
7. Serum ferritin level is decreased to less than 12
µg/L (normal: 18-300 µg/L). A low serum ferritin
indicates iron deficiency; however, ferritin, which is
an acute phase reactant, may be elevated in the
presence of infection, inflammation, and malignancy.
8. Iron binding capacity (IBC) is increased, usually to
more than 375 µg/dL (normal: up to 300 µg/dL).
9. Serum iron is decreased, often to less than 60
µg/dL (normal: 100 µg/dL).
DIAGNOSIS (cont)
10. Transferrin saturation is decreased to less than
16%.
11. Erythrocyte protoporphyrin is increased.
12. Bone marrow biopsy is not usually necessary but
would demonstrate absence of iron stores. In anemia
of chronic disease, serum iron may be low but the
IBC is not elevated.
13. Lead Testing will help rule out lead poisoning.
TREATMENT
• In the nonmenstruating adult, iron deficiency could represent GI
blood loss; therefore, appropriate workup should be initiated
and the cause addressed.
• With the initiation of iron replacement therapy, reticulocyte
count should rise within a week and a 2 g/dL hemoglobin
increase should be seen in 3 weeks.
• To replenish the stores, continue replacement for 6 months.
• Treatment failures are due to noncompliance, malabsorption,
inadequate dosing, ongoing blood loss, or incorrect diagnosis.
TREATMENT (cont)
Iron replacement
• Oral. Ferrous sulfate
• GI side effects are dose related and include nausea
and constipation.
• Drugs such as histamine-2 blockers, proton pump
inhibitors, antacids, and methyldopa reduce
absorption.
• For children, iron supplements in the form of drops,
elixir, and syrup are available. Liquid preparations are
given by dropper or straw to prevent staining of teeth.
TREATMENT (cont)
Parenteral.
• In the presence of severe side effects, GI
intolerance, or poor absorption due to
inflammatory bowel disease, iron may be given
parenterally.
•Intravenous route is recommended and iron
dextran (Imferon 50 mg/mL) is preferred.
TREATMENT (cont)
Blood Transfusion
•If Hb < 7 g/dl
TREATMENT (cont)
Prevention
•Breast milk or formula should be encouraged
during the first year of life, as cow's milk is a poor
source of iron.
•Along with a diet rich in iron, supplemental iron
should be provided when the requirement is high,
such as during infancy and growth spurts, in people
who donate blood on a frequent basis, in
menstruating girls and women, and in pregnant and
lactating women.
Erythropoiesis,Anemia,Iron Deficiency Anemia by Dr. Sookun Rajeev Kumar

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Erythropoiesis,Anemia,Iron Deficiency Anemia by Dr. Sookun Rajeev Kumar

  • 1. ERYTHROPOIESIS CLASSIFICATION OF ANEMIA & IRON DEFICIENCY ANEMIA Dr. Sookun Rajeev K (MD) Dept of General Medicine Anna Medical College
  • 3. ERYTHROPOIESIS •It is the process by which progenitor cells in the marrow proliferate, differentiate into Normoblasts and mature into anucleated reticulocytes which enter the circulation. •Normal life span of RBC 110-120 days
  • 4. ERYTHROPOIESIS (cont) Hematinics necessary for Red Cell formation: 1. Aminoacids for synthesis of chains of globin 2. Iron for Hb synthesis 3. Vitamin B12 and folic acid for nucleic acid synthesis of erythroid precursors 4. Zinc 5. Vitamin C to raise absorption of iron from ferric to ferrous state
  • 5. ERYTHROPOIESIS (cont) 6. Vitamin E for maintainance of integrity of red cells 7. Copper helps transfer of iron cells to plasma with aid of ceruloplasmin 8. Thyroxine 9. Androgen 10.Cobalt trace element as part of vit B12
  • 6. ERYTHROPOIESIS (cont) Process of Erythropoiesis Erythropoiesis is regulated by erythropoietin, vitamin B12, Folic Acid and Iron
  • 7. NORMAL HEMOGLOBIN VALUES AGE HEMOGLOBIN 1 - 3 days 14.5 – 22.5g/dl 6 mo - 2 yrs 10.5 – 13.5 g/dl 12 yrs – 18 yrs male 13.0 – 16.0 g/dl 12 yrs – 18 yrs female 12.0 – 16.0 g/dl > 18 yrs male 13.5 – 17.5 g/dl >18 yrs female 12.0 – 16.0 g/dl
  • 8. ANEMIA Definition: Anemia is defined as a reduction in Hct or Hb concentration. <13.5 g/dl in adult males <12.0 g/dl in adult females <11.0 g/dl in pregnant women <10.5 g/dl in infants 6 mn to 2 yrs <11.5 g/dl in children 2 yrs to 12 yrs
  • 9. ANEMIA (cont) • When red cell mass (as measured by Hb or less precisely by Hct) decreases, several compensatory mechanisms maintain oxygen delivery to the tissues. These mechanisms include: Increased cardiac output (heart rate and stroke volume) Increased extraction ratio Rightward shift of the oxyhemoglobin curve (increased 2,3-diphosphoglycerate [2,3-DPG]) Expansion of plasma volume
  • 10. ANEMIA (cont) • If anemia develops rapidly, symptoms are more likely to be present, because there is little time for compensatory mechanisms. When onset is gradual, compensatory mechanisms are able to maintain oxygen delivery, and symptoms may be minimal or absent.
  • 11. CLASSIFICATION OF ANEMIA 1. Microcytic Anemias (MCV <80 fl) • Anemia of chronic disease :Decreased iron and decreased TIBC; increased ferritin • Sideroblastic anemia: Increased iron and normal TIBC; increased ferritin. Peripheral smear shows basophilic stippling and ringed sideroblasts. • Iron deficiency anemia Decreased iron and increased TIBC. Ferritin<12 µg/L is very suggestive of iron deficiency. • Thalassemia Very low MCV (usually <70 fL); normal iron studies. The peripheral smear may reveal basophilic stippling. Hemoglobin electrophoresis is needed for diagnosis.
  • 12. CLASSIFICATION OF ANEMIA 2. Normocytic Anemias (MCV >80 fl,MCV <100 fl) •Hemorrhage Look for source of blood loss, perform a Hemoccult's stool •Glucose-6-phosphate deficiency •Autoimmune hemolytic anemia Positive Coombs •Membranopathies Hereditary spherocytosis with splenomegaly on physical examination
  • 13. CLASSIFICATION OF ANEMIA 3. Macrocytic Anemias (MCV >100 fl) •Vitamin B12 or folate deficiency Low serum vitamin B12 and folate levels. The peripheral smear reveals hypersegmented neutrophils. Vitamin B12 deficiency may also have neurologic findings. •Liver disease Elevated liver function tests, aspartate aminotransferase, and alanine aminotransferase. The peripheral smear may reveal target and spur cells.
  • 14. CLASSIFICATION OF ANEMIA ~400 types of Anemia Iron Deficiency Anemia Myeloblastic Anemia Pernicious Anemia Hemorrhagic Anemia Hemolytic Anemia Thalassemia Aplastic Anemia
  • 15. CAUSES OF IRON DEFICIENCY ANEMIA Iron deficiency results in a defective synthesis of hemoglobin and smaller red cells (microcytic) with less hemoglobin within the cell (hypochromic). In Children Increased requirements Inadequate dietary iron Malnutrition Low iron stores Eating disorders Pica Lead poisoning.
  • 16. CAUSES OF IRON DEFICIENCY ANEMIA In Adults Gastrointestinal (GI) blood loss are the use of nonsteroidal anti-inflammatory drugs, Peptic ulcer disease Angiodysplasia Diverticulosis Malignancy Rarely, parasites such as Hookworms. Frequent blood donations and phlebotomies, surgical procedures
  • 17. CAUSES OF IRON DEFICIENCY ANEMIA In Females, Menstrual disorders, Pregnancy Lactation • The daily loss of iron in an adult is about 1 mg, and menstrual loss can be an additional 20 mg per month. • Normally less than 10% of the daily dietary intake of iron is absorbed.
  • 18. HISTORY FROM PATIENT A.The evaluation should determine if the anemia is of acute or chronic onset, and clues to any underlying systemic process should be sought. B. A history of drug exposure, blood loss, or a family history of anemia should be sought. C.Lymphadenopathy, hepatic or splenic enlargement, jaundice, bone tenderness, neurologic symptoms or blood in the feces should be sought.
  • 19. SIGNS Tachycardia Systolic murmur Dry skin Dysphagia from pharyngeal and esophageal webs may also be present.
  • 20. SIGNS Pallor of the conjunctiva, lips, nail beds
  • 22. SIGNS Nail changes such as brittle and spoon-shaped nails (koilonychia).
  • 27. DIAGNOSIS 1. The test result would depend on the stage of development of iron deficiency. 2. The classic hypochromic microcytic picture develops when iron stores are exhausted. 3. Anisocytosis, poikilocytosis, and target cells may be present on the peripheral smear. 4. Increased red cell distribution width with a low mean corpuscular volume is suggestive of iron deficiency anemia.
  • 28. DIAGNOSIS (cont) 1. Full Blood Count Hemoglobin level The MCV is normal in early iron deficiency. As the hematocrit falls below 30%, hypochromic microcytic cells appear, followed by a decrease in the MCV.
  • 29. DIAGNOSIS (cont) 2. Peripheral Blood Smear 3. Reticulocyte count 4. Urine Micros 5. Stool for FOB 6. Stool for Ova, Cysts & Parasite
  • 30. DIAGNOSIS (cont) 7. Serum ferritin level is decreased to less than 12 µg/L (normal: 18-300 µg/L). A low serum ferritin indicates iron deficiency; however, ferritin, which is an acute phase reactant, may be elevated in the presence of infection, inflammation, and malignancy. 8. Iron binding capacity (IBC) is increased, usually to more than 375 µg/dL (normal: up to 300 µg/dL). 9. Serum iron is decreased, often to less than 60 µg/dL (normal: 100 µg/dL).
  • 31. DIAGNOSIS (cont) 10. Transferrin saturation is decreased to less than 16%. 11. Erythrocyte protoporphyrin is increased. 12. Bone marrow biopsy is not usually necessary but would demonstrate absence of iron stores. In anemia of chronic disease, serum iron may be low but the IBC is not elevated. 13. Lead Testing will help rule out lead poisoning.
  • 32. TREATMENT • In the nonmenstruating adult, iron deficiency could represent GI blood loss; therefore, appropriate workup should be initiated and the cause addressed. • With the initiation of iron replacement therapy, reticulocyte count should rise within a week and a 2 g/dL hemoglobin increase should be seen in 3 weeks. • To replenish the stores, continue replacement for 6 months. • Treatment failures are due to noncompliance, malabsorption, inadequate dosing, ongoing blood loss, or incorrect diagnosis.
  • 33. TREATMENT (cont) Iron replacement • Oral. Ferrous sulfate • GI side effects are dose related and include nausea and constipation. • Drugs such as histamine-2 blockers, proton pump inhibitors, antacids, and methyldopa reduce absorption. • For children, iron supplements in the form of drops, elixir, and syrup are available. Liquid preparations are given by dropper or straw to prevent staining of teeth.
  • 34. TREATMENT (cont) Parenteral. • In the presence of severe side effects, GI intolerance, or poor absorption due to inflammatory bowel disease, iron may be given parenterally. •Intravenous route is recommended and iron dextran (Imferon 50 mg/mL) is preferred.
  • 36. TREATMENT (cont) Prevention •Breast milk or formula should be encouraged during the first year of life, as cow's milk is a poor source of iron. •Along with a diet rich in iron, supplemental iron should be provided when the requirement is high, such as during infancy and growth spurts, in people who donate blood on a frequent basis, in menstruating girls and women, and in pregnant and lactating women.