The hematopoietic system

Question 1

What are the most important diseases of the hematopoietic and lymphoid
systems?

Answer 1

• Anemia
• Polycythemia
• Leukemia
• Leukopenia
• Non-Hodgkin lymphoma
• Hodgkin lymphoma
• Multiple myeloma
• Lymphopenia and immunodeficiency diseases
• Bleeding disorders

Question 2

Define anemia.

Answer 2

Anemia can be defined as a decrease in the red blood cell (RBC) mass and the hemoglobin
content in the blood.

Question 3

It may be diagnosed by the demonstration of decreased values of certain
parameters, which are?

Answer 3

Hemoglobin concentration
- Hematocrit
- Erythrocyte count
One should note that overhydration due to fluid retention may expand plasma volume,
and fluid loss may contract plasma volume. These conditions are called hemodilution and
hemoconcentration, respectively. Hemodilution should not be confused with anemia.

Question 4

What are the best hematologic tests for diagnosing anemia?

Answer 4

1.-RBC count
○ Hemoglobin
○ Hematocrit
2.- RBC indices
○ Mean cell volume (MCV)
○ Mean corpuscular hemoglobin (MCH)
○ Mean corpuscular hemoglobin concentration (MCHC)
3.- RBC distribution width
4.- White blood cell (WBC) count
5.- Platelet count
6.- Cell morphology& Reticulocyte count 7.-Iron supply studies ○ Serum iron ○ Total iron-binding capacity ○ Serum ferritin, marrow iron content 8.- Bone marrow examination ○ Aspirate ○ Biopsy

Question 5

List three major groups of anemia according to their etiology and
pathogenesis.

Answer 5

1. • Anemia due to blood loss
2. -Anemia due to increased rate of RBC destruction (hemolytic anemia)
3. -Anemia due to impaired RBC production

Question 6

Anemia due to blood loss can be classified in?

Answer 6

○ Acute blood loss: massive bleeding from ruptured vessels, wounds, and trauma
○ Chronic blood loss: bleeding lesions of gastrointestinal tract and gynecologic
disturbances

Question 7

Anemia due to increased rate of RBC destruction can be classified in?

Answer 7

○ Intrinsic (intracorpuscular) abnormalities of red cells:
- Hereditary
- Red cell membrane disorder: hereditary spherocytosis
- Red cell enzyme deficiencies: glucose-6-phosphate dehydrogenase deficiency
- Disorders of hemoglobin synthesis: sickle cell disease and thalassemia syndromes
- Acquired
- Paroxysmal nocturnal hemoglobinuria
○ Extrinsic (extracorpuscular)
- Antibody mediated: transfusion reaction, erythroblastosis fetalis, and
immunohemolytic anemia
- Mechanical injury of RBCs: microangiopathic hemolytic anemia

Question 8

Anemia due to impaired RBC production can be classified in?

Answer 8

○ Disturbance of proliferation and differentiation of stem cells; aplastic anemia and pure
RBC aplasia
○ Disturbance of proliferation and maturation of erythroblasts
- Defective DNA synthesis: megaloblastic anemia
- Defective hemoglobin synthesis: iron deficiency and thalassemia
- Unknown or multiple mechanisms: anemia of chronic infections and myelophthisic
anemia

Question 9

How are anemias classified according to the red cell size?

Answer 9

& According to red cell size
○ Microcytic (small)
○ Normocytic (normal)
○ Macrocytic (large)

Question 10

How are anemias classified according to their
hemoglobin content?

Answer 10

• According to degree of hemoglobinization, reflected in the color of red cells
  ○ Hypochromic (decreased)
  ○ Normochromic (normal)

Question 11

How are anemias classified according to the red cell shape?

Answer 11

Question 12

How are anemias classified according to the red cell shape EXAMPLES of diseases?

Answer 12

Question 13

Define hematocrit.

Answer 13

- The ratio of RBCs to serum expressed in percentages:
○ In anemia, hematocrit is low, whereas in polycythemia it is high
○ Normal values: men, 39% to 49%; women, 33% to 43%

Question 14

Define Mean cell volume (MCV) of erythrocytes.

Answer 14

○ The average calculated volume of a single RBC (hematocrit/erythrocyte count)
○ On the basis of MCV, anemias may be defined as microcytic, normocytic, or macrocytic
○ Normal values: 76 to 100 mm3.

Question 15

Define Mean Corpuscular Hemoglobin (MCH).

Answer 15

○ The average content of hemoglobin in each RBC (hemoglobin/erythrocyte count)
○ According to MCH, anemia can be defined as hypochromic or normochromic
○ Normal values: 27 to 33 pg

Question 16

Define Mean Corpuscular Hemoglobin Concentration (MCHC).

Answer 16

○ The average concentration of hemoglobin in a given volume of packed RBCs
(hemoglobin/hematocrit)
○ According to MCHC, anemia may be defined as hypochromic, normochromic, or
hyperchromic
○ Normal values: 33 to 37 g/dL
○ In contrast to MCH, MCHC considers the size of erythrocytes, therefore diminishing the
possibility of spurious results in case of low hemoglobin concentration or a decrease
in erythrocyte size.

Question 17

Discuss how reticulocyte counts are used in clinical practice.

Answer 17

The reticulocyte is a stage of RBC maturation, normally present in both the marrow and the
blood. Under normal conditions, the peripheral blood contains less than 1.5% reticulocytes,
but in some anemic patients, their number may be increased. Reticulocyte count is used to
assess the capacity of the bone marrow to increase RBC production in response to increased
demand. On the basis of the reticulocyte count, anemias may be classified as hypoproliferative,
normoproliferative, and hyperproliferative.

Question 18

What is Hypoproliferative Anemia?

Answer 18

Patients with anemia caused by defects in erythrocyte proliferation
or maturation tend to have low reticulocyte counts. Patients suffering from pernicious
anemia have low reticulocyte count, which will, however, increase after vitamin B12
treatment.

Question 19

What is Normoproliferative or hyperproliferative Anemia?

Answer 19

Patients with anemia caused by decreased
survival of erythrocytes with a normal bone marrow proliferative response often exhibit
increased peripheral blood reticulocytes. If the degree of reticulocytosis is adequate to
replace the loss of erythrocytes, the anemia is said to be compensated.

Question 20

List signs and symptoms common to all forms of anemia.

Answer 20

• Pale skin and mucosa (e.g., conjunctiva)
• Easy fatigability and dyspnea on mild exertion
• Koilonychia, a spoon-shaped concavity of the nails, associated with brittle nails; feature of
  prolonged anemia that is rarely seen today
• Central nervous system hypoxia causing headaches, dim vision, and drowsiness

Question 21

Are there any pathologic tissue findings characteristic of anemia in general?

Answer 21

No. Most of the tissue changes caused by anemia are nonspecific. These findings include
consequences of prolonged mild ischemia and hypoxia, such as fatty change of liver and heart
cells. Prolonged and severe anemia leads to a loss of neurons in the brain, but such a loss
cannot be readily recognized in routine histologic sections.

Question 22

Describe the typical hematologic changes following acute massive blood loss.

Answer 22

Massive blood loss may result in shock and even death. If the person survives, the blood
volume is rapidly restored by entry of water from the interstitial spaces into the circulation. This
redistribution of water results in hemodilution, which lowers the hematocrit. The RBC counts
performed at this point will usually show anemia, which is typically normocytic and
normochromic. Thrombocytosis and leukocytosis may be found in peripheral blood because of
mobilization of these cells from the marginal pools. Reactive reticulocytosis occurs a few days
later. It is mediated by erythropoietin released from the kidneys in response to low oxygen
tension in the blood depleted of RBCs. Reticulocytosis will reach its peak 7 to 10 days after
hemorrhage and may be as high as 10% to 15% (i.e., 10 times higher than normal).

Question 23

How does chronic blood loss cause anemia?

Answer 23

Chronic blood loss causes a loss of iron, but significant anemia occurs only when the rate of
loss exceeds the regenerative capacity of the bone marrow or when iron reserves are
markedly depleted. Anemia of chronic blood loss is common in menstruating women, who
lose approximately 70 mL of blood during every menstruation. Frequent pregnancies and
childbirth are other important causes of anemia. Gastrointestinal diseases are the most
common cause of iron-deficiency anemia in men. Nevertheless, in all patients with irondeficiency
anemia, testing of stools and the urine for occult blood loss should be performed.

Question 24

List the three main features common to all forms of hemolytic anemia.

Answer 24

• Premature destruction of erythrocytes, which live less than the normal 120 days
• Accumulation of the hemoglobin degradation products (e.g., hemosiderin) in phagocytic cells
• A marked increase in erythropoietin stimulating compensatory erythropoiesis within the
  bone marrow

Question 25

What is intravascular hemolysis?

Answer 25

Intravascular hemolysis: Significant lysis of erythrocytes rarely occurs within the vascular spaces. In intravascular hemolysis, normal erythrocytes are damaged by: › Mechanical injury - Mechanical cardiac valves - Thrombi within microcirculation › Complement fixation to red cells - Transfusion of mismatched blood › Exogenous toxic factors or infections - Falciparum malaria - Clostridial sepsis

Question 26

What is extravascular hemolysis

Answer 26

Extravascular hemolysis: Most frequently, the premature destruction of erythrocytes occurs within the mononuclear phagocyte system of the spleen and liver. In extravascular hemolysis, erythrocytes are destroyed because: › They are rendered eeforeignff by autoantibodies that attach to them in autoimmune hemolytic anemia. › They become less deformable as in sickle cell anemia or hereditary spherocytosis. In both forms of hemolysis, there is anemia and jaundice. Hemoglobinemia and hemoglobinuria occur only in intravascular hemolysis. Hypertrophy of the mononuclear phagocyte system and consequent splenomegaly are seen only in extravascular hemolysis.

Question 27

What are the main features of intravascular hemolysis?

Answer 27

Jaundice Hemoglobinemia Methemalbuminemia Hemoglobinuria Hemosiderinuria

Question 28

Why is jaundice featured in intravascular hemolysis?

Answer 28

Jaundice: It is related to the excessive formation of unconjugated bilirubin from the heme portion of hemoglobin. Unconjugated bilirubin is bound to albumin and does not appear in urine.

Question 29

Why is hemoglobinemia featured in intravascular hemolysis?

Answer 29

Hemoglobinemia: It results from the release of free hemoglobin released from RBCs. Free hemoglobin binds to haptoglobin, which prevents its excretion into urine. Hemoglobin– haptoglobin complex is rapidly cleared by the mononuclear phagocyte system. Accordingly,the blood concentration of haptoglobin will be reduced. Decreased serum haptoglobin is areliable sign of intravascular hemolysis. ## Footnote

Question 30

Why is Methemalbuminemia featured in intravascular hemolysis?

Answer 30

Methemalbuminemia: When the serum haptoglobin is depleted, the unbound or free hemoglobin is in part rapidly oxidized to methemoglobin, which binds to albumin forming methemalbumin.

Question 31

Why is hemoglobinuria featured in intravascular hemolysis?

Answer 31

Hemoglobinuria: Hemoglobin in urine appears after the haptoglobin binding capacity has been exceeded and the free hemoglobin is filtered through the glomeruli. Both hemoglobin and methemoglobin are excreted through the kidneys, imparting a red-brown color to the urine.

Question 32

Why is hemosiderinuria featured in intravascular hemolysis?

Answer 32

Hemosiderinuria: Hemosiderin in urine is derived from hemoglobin degradation in the renal tubules.

Question 33

What is the mechanism of erythroid hyperplasia of the bone marrow in hemolytic anemia?

Answer 33

All forms of hemolytic anemia are accompanied by premature destruction of erythrocytes. The resulting anemia and lowered oxygen saturation of blood stimulate increased production of erythropoietin in the kidneys, which leads to an increase in the number of normoblasts in the bone marrow and prominent reticulocytosis in the peripheral blood.

Question 34

Name the common pathologic tissue findings common to all forms of chronic hemolytic anemia.

Answer 34

- Increase in the number of normoblasts in the bone marrow - Prominent reticulocytosis in the peripheral blood - Formation of pigment gallstones (cholelithiasis) caused by elevated levels of bilirubin when it is excreted through the liver - Hemosiderosis due to hemosiderin accumulation in the mononuclear phagocyte system in long-term anemias (Hemosiderin accumulation is due in part to hemosiderin released from damaged RBCs and in part to the transfusions of blood that such patients typically receive.)

Question 35

What is the difference between anemia caused by extrinsic factors (extracorpuscular defects) and anemia caused by intrinsic factors (intracorpuscular defects)?

Answer 35

**1.- Extracorpuscular** ○ Extrinsic underlying cause ○ Acquired disorders (i.e., antibody mediated, mechanical trauma to red cells, infections, and chemical injury) **2.- Intracorpuscular** ○ Hereditary disorders (i.e., red cell membrane disorders, red cell enzyme deficiencies, and disorders of hemoglobin synthesis) ○ Acquired disorders (i.e., paroxysmal nocturnal hemoglobinuria)

Question 36

KEY POINTS HEMATOLOGY AND RBC DISORDERS.

Answer 36

1. Hematology covers diseases of red blood cells (RBCs), platelets, blood coagulation factors, leukocytes, and lymphoid cells. 2. Anemia is a decrease in the red cell mass and hemoglobin content of the blood, reducing the capacity of the blood to transport oxygen. 3. Anemia can be classified etiologically into three groups: anemia due to blood loss, hemolytic anemia, and anemia due to impaired RBC production.4. Hemolytic anemias develop due to inherent RBC defects or due to antibodies and other extracorpuscular causes. 5. RBC production can be impaired due to deficiency of iron, vitamin B12, and folic acid or as a consequence of bone marrow failure in aplastic anemia. 6. Polycythemia vera can occur in two forms: as polycythemia vera, which is a neoplastic disorder, and as a secondary polycythemia, which is related to excessive stimulation of RBC precursors by erythropoietin.

Question 37

What is hereditary spherocytosis?

Answer 37

``` Hereditary spherocytosis (HS) is caused by several inherited defects in the red cell membrane skeleton that render the RBCs spheroid (round) and less deformable during their passage through the splenic sinusoids. Spherical RBCs are thus more prone to splenic sequestration and destruction, which lead to intracorpuscular hemolysis. ```