Normochromic Normocytic Anemia (except hemolytic anemia) Megaloblastic Anemia

Question 1

NORMOCHROMIC NORMOCYTIC ANEMIAS

Answer 1

Aplastic anemia

Acute blood loss anemia

Question 2

APLASTIC ANEMIA

Answer 2

Aplastic anemia results from red blood cells’ impaired
production in the marrow.

This results in a markedly hypocellular marrow and
varying degrees of anemia, granulocytopenia, and
thrombocytopenia = pancytopenia

Question 3

ETIOLOGIC CLASSIFICATION OF

APLASTIC ANEMIA

Answer 3

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Question 4

LABORATORY FEATURES of APLASTIC ANEMIA

Answer 4

1. pancytopenia
2. normochromic normocytic anemia (macrocytosis may result from the high levels of erythropoietin)
   reticulocyte count is less than 1.0 percent and may be
   zero.
3. the absolute neutrophil count is the most important
   prognostic feature, with a count of less than 500/µl (0.5 × 109/liter) associated with increased risk of infections and less than 200/µl (0.2 × 109/liter) associated with a dire prognosis.
4. the marrow aspirate typically contains empty fatty spaces and relatively few hematopoietic cells.

Question 5

ACUTE BLOOD LOSS ANEMIA

Answer 5

• With precipitous hemorrhage the immediate effects of volume depletion are more important than the loss of circulating red blood cells.
• Only when blood loss is relatively slow and the total blood volume is maintained by natural or artificial means does anemia become a problem.

Question 6

ACUTE BLOOD LOSS ANEMIA STAGES

Answer 6

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Question 7

MEGALOBLASTIC ANEMIA

Answer 7

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Question 8

Laboratory features of Megaloblastic Anemia

Answer 8

1. Marrow
2. Peripheral blood smear
3. Blood count
4. Clinical chemistry changes

Question 9

Marrow

Answer 9

1. Aspirated marrow shows megaloblastic changes, especially in the erythroid series.
2. Sideroblasts are increased in number and contain increased numbers of iron granules.

Question 10

Peripheral blood smear

Answer 10

1. Erythrocytes are large and oval
2. A few reticulocyte.
3. Red cells with megaloblastic nuclei may appear in the blood in severe cases
4. Neutrophil nuclei often have more than five lobes

Question 11

Blood count

Answer 11

• The anemia is macrocytic (MCV = 100 to 150 fl or more), although coexisting iron deficiency, thalassemia trait, or inflammation can prevent macrocytosis.
• Slight macrocytosis is often the earliest sign of megaloblastic anemia.
• The reticulocyte count is low
• Neutropenia and trombocitopenia in severe cases of cobalamin/folate deficiency

Question 12

Clinical chemistry changes

Answer 12

Iron, and ferritin levels are increased

Plasma bilirubin (unconjugated bilirubin) levels are elevated

Serum LDH-1 and LDH-2 are markedly elevated, increasing with the severity of the anemia.

Question 13

NUTRITION

VITAMIN B12 – COBALAMIN (CBL)

Answer 13

1. The Dietary Reference Intake for an adult ranges from 1 to 5 µg per day
2. Animal protein is the major dietary Cbl source: animal parenchymal organs (>10 µg Cbl per 100 g), muscle, fish, milk products and egg yolk
3. Cbl liver storage = 3-5 mg
4. Daily Cbl losses : urine (>7% of the dietary Cbl), feces,
   epithelial = 0.1% of the liver storage

Question 14

ABSORPTION

VITAMIN B12 – COBALAMIN (CBL)

Answer 14

1. In the stomach, peptic digestion at low pH is required for Cbl release from food protein; also in the stomach the intrinsic factor (IF) is synthesized by gastric parietal cells
2. Released by proteolysis, Cbl binds a high-affinity
   Cbl-binding protein called R protein (also called haptocorrin)
3. In the duodenum, at alkaline pH, pancreatic proteases release Cbl from R protein which then binds to IF, to form a complex (IF/Cbl)
4. IF has two binding sites: one for Cbl and another for the ileal IF-Cbl receptor called cubilin; In the absence of IF, <2% of ingested Cbl is absorbed, whereas in its presence, 70% is absorbed.
5. More than 90% of recently absorbed or injected Cbl is bound to transcobalamin II (TC II), which is a specific transport protein for delivery of Cbl to tissues;

Question 15

COBALAMIN DEFICIENCY

Answer 15

1. DECREASED UPTAKE CAUSED BY IMPAIRED ABSORPTION
2. DIETARY COBALAMIN DEFICIENCY.
3. INCREASED CONSUMPTION OF COBALAMIN

Question 16

DECREASED UPTAKE CAUSED BY
IMPAIRED ABSORPTION (I)

Answer 16

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Question 17

2. DIETARY COBALAMIN DEFICIENCY

Answer 17

a) Dietary cobalamin deficiency is very unusual. It occurs mainly in vegetarians who also avoid dairy products and eggs (vegans). Low serum cobalamin levels occur in 50 to 60% of this group. Breast-fed infants of vegan mothers may also develop cobalamin deficiency. Cobalamin deficiency in
vegans presents with mild megaloblastic anemia and
neurologic disturbances.

b) Cobalamin deficiency may occur in severe general
malnutrition.

Question 18

3. INCREASED CONSUMPTION OF

COBALAMIN

Answer 18

a) Cronic hemolytic anemias - increased marrow cell
turnover

b) Cancers - elevated number of mitosis leads to
cobalamin consumption

Question 19

FOLIC ACID NUTRITION

Answer 19

1 ) Folates are widely distributed in nature: leafy vegetables (spinach,
lettuce, broccoli, beans), fortified grain, fruits (bananas, melons, lemons), yeast, mushrooms, and animal protein (liver, kidney) are rich sources of folate

2) The minimum daily requirement of folate is 50 µg; recommended dietary allowance is 400 – 600 µg
3) Folate storage = 8-20 mg
4) Daily folate losses : urine, feces, epithelial = 1-2 % of the folate storage

Question 20

FOLIC ACID ABSORPTION

Answer 20

small intestine has a large capacity to absorb folate especially duodenum and jejunum through passive diffusion

Question 21

FOLIC ACID DEFICIENCY

Answer 21

1. DECREASED INTAKE CAUSED BY POOR
   NUTRITION
2. DECREASED INTAKE CAUSED BY IMPAIRED
   ABSORPTION
3. INCREASED FOLATE REQUIREMENTS

Question 22

DECREASED INTAKE CAUSED BY
POOR NUTRITION
FOLIC ACID

Answer 22

Infants raised on goat’s milk, which is folate-poor

Malnourished individuals - typically the old, the poor and the alcoholic.

In alcoholic cirrhosis, megaloblastic anemia is usually caused by
folate deficiency. In addition, alcohol may acutely depress the
serum folate, even if folate storages are full, and will accelerate
the development of megaloblastic anemia in someone with early folate deficiency.

Question 23

DECREASED INTAKE CAUSED BY
IMPAIRED ABSORPTION
FOLIC ACID

Answer 23

1. Celiac disease related to the ingestion of wheat gluten.
2. Tropical Sprue is endemic in the West Indies, southern India, parts of southern Africa, and Southeast Asia. Tropical sprue is rapidly corrected by folate therapy. The etiology of tropical sprue is unknown, although infection is suggested by the response of the disease to antibiotics.
3. Other Intestinal Disorders: regional enteritis, resections of the small intestine, in lymphomatous or leukemic infiltration of the small intestine

Question 24

INCREASED FOLATE REQUIREMENTS

Answer 24

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Question 25

HEMOLYTIC ANEMIAS

Answer 25

Hemolytic anemias result from an increased rate of red blood cells destruction while the ability of the bone marrow to respond is unimpaired.

Question 26

CORPUSCULAR HEMOLYTIC ANEMIAS

Answer 26

HEREDITARY SPHEROCYTOSIS

SICKLE CELL ANEMIA

THE THALASSEMIAS

Question 27

HEREDITARY SPHEROCYTOSIS (HS)

Answer 27

Defects in several membrane proteins, including ankyrin,
band 3 and spectrin which lead to loss of membrane surface
area - accounting for :

• the spherical shape
• decreased deformability of the erythrocyte

Splenic trapping of nondeformable spherocytes, followed by conditioning and destruction of these abnormal erythrocytes, is the cause of hemolysis experienced by HS patients.

The spleen plays an important role in hemolysis, but secondary to the basic defect of the erythrocyte membrane.