The hematopoietic system Flashcards
What are the most important diseases of the hematopoietic and lymphoid
systems?
- Anemia
- Polycythemia
- Leukemia
- Leukopenia
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Multiple myeloma
- Lymphopenia and immunodeficiency diseases
- Bleeding disorders
Define anemia.
Anemia can be defined as a decrease in the red blood cell (RBC) mass and the hemoglobin
content in the blood.
It may be diagnosed by the demonstration of decreased values of certain
parameters, which are?
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.
What are the best hematologic tests for diagnosing anemia?
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
List three major groups of anemia according to their etiology and
pathogenesis.
- Anemia due to blood loss
- -Anemia due to increased rate of RBC destruction (hemolytic anemia)
- -Anemia due to impaired RBC production
Anemia due to blood loss can be classified in?
○ Acute blood loss: massive bleeding from ruptured vessels, wounds, and trauma
○ Chronic blood loss: bleeding lesions of gastrointestinal tract and gynecologic
disturbances
Anemia due to increased rate of RBC destruction can be classified in?
○ 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
Anemia due to impaired RBC production can be classified in?
○ 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
How are anemias classified according to the red cell size?
& According to red cell size
○ Microcytic (small)
○ Normocytic (normal)
○ Macrocytic (large)
How are anemias classified according to their
hemoglobin content?
- According to degree of hemoglobinization, reflected in the color of red cells
○ Hypochromic (decreased)
○ Normochromic (normal)
How are anemias classified according to the red cell shape?
How are anemias classified according to the red cell shape EXAMPLES of diseases?
Define hematocrit.
- 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%
Define Mean cell volume (MCV) of erythrocytes.
○ 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.
Define Mean Corpuscular Hemoglobin (MCH).
○ 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
Define Mean Corpuscular Hemoglobin Concentration (MCHC).
○ 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.
Discuss how reticulocyte counts are used in clinical practice.
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.
What is Hypoproliferative Anemia?
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.
What is Normoproliferative or hyperproliferative Anemia?
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.
List signs and symptoms common to all forms of anemia.
- 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
Are there any pathologic tissue findings characteristic of anemia in general?
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.
Describe the typical hematologic changes following acute massive blood loss.
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).
How does chronic blood loss cause anemia?
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.
List the three main features common to all forms of hemolytic anemia.
- 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
What is intravascular hemolysis?
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
What is extravascular hemolysis
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 eeforeignff 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.
What are the main features of intravascular hemolysis?
Jaundice
Hemoglobinemia
Methemalbuminemia
Hemoglobinuria
Hemosiderinuria
Why is jaundice featured in intravascular hemolysis?
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.
Why is hemoglobinemia featured in intravascular hemolysis?
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.
Why is Methemalbuminemia featured in intravascular hemolysis?
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.
Why is hemoglobinuria featured in intravascular hemolysis?
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.
Why is hemosiderinuria featured in intravascular hemolysis?
Hemosiderinuria: Hemosiderin in urine is derived from hemoglobin degradation in
the renal tubules.
What is the mechanism of erythroid hyperplasia of the bone marrow in
hemolytic anemia?
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.
Name the common pathologic tissue findings common to all forms of chronic
hemolytic anemia.
- 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.)
What is the difference between anemia caused by extrinsic factors
(extracorpuscular defects) and anemia caused by intrinsic factors
(intracorpuscular defects)?
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)
KEY POINTS HEMATOLOGY AND RBC DISORDERS.
- Hematology covers diseases of red blood cells (RBCs), platelets, blood coagulation factors,
leukocytes, and lymphoid cells. - Anemia is a decrease in the red cell mass and hemoglobin content of the blood, reducing the
capacity of the blood to transport oxygen. - 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.
What is hereditary spherocytosis?
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.
