DISEASES OF
HEMATOLYMPHOID SYSTEM
Manar hajeer, MD
RED CELL DISORDERS
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Anemia is a reduction in the oxygen-transporting
capacity of blood, which usually stems from a
reduction of the total circulating red cell mass to
below-normal amounts.
Anemia can result from excessive bleeding,
increased red cell destruction, or decreased red
cell production.
BLOOD LOSS (HEMORRHAGE):
Acute: trauma
 Chronic: lesions of gastrointestinal tract,
gynecologic disturbances.
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INCREASED DESTRUCTION (HEMOLYTIC
ANEMIAS)
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Intrinsic (intracorpuscular) abnormalities
Hereditary
Membrane abnormlities spherocytosis.
Enzyme deficiencies : glucose-6-phosphate dehydrogenase.
Disorders of hemoglobin synthesis
Deficient globin synthesis: thalassemia syndromes
Structurally abnormal globin synthesis
(hemoglobinopathies): sickle cell anemia,
Extrinsic (extracorpuscular)
Antibody mediated
Mechanical trauma to red cells
Infections: malaria
IMPAIRED RED CELL PRODUCTION
Disturbance of proliferation and
differentiation of stem cells: aplastic
anemia, pure red cell aplasia, anemia of renal
failure,
 Disturbance of proliferation and
maturation of erythroblasts
 Defective DNA synthesis: deficiency or impaired
utilization of vitamin B12 and folic acid
(megaloblastic anemias)
 Defective hemoglobin synthesis
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Deficient heme synthesis: iron deficiency
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Deficient globin synthesis: thalassemias
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Anemia of renal failure
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1. ANEMIA OF BLOOD LOSS(HEMORRHAGE)
With acute blood loss, the immediate threat to the
patient is hypovolemia (shock) rather than
anemia.
- Is characterized by normocytic and normochromic RBCs
- Recovery from acute blood loss anemia is enhanced by a rise
in the erythropoeitin levels, which stimulates increased red
cell production within several days.
- With chronic blood loss, iron stores are gradually depleted
and the result is iron defficiency anemia.
2. THE HEMOLYTIC ANEMIAS
Are associated with accelerated destruction of red cells
Normal life span of RBCs is 120 days.
- Destruction can be:
a. Intrinsic inherited red cell defects.,
b. External acquired factors.
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General features of all hemolytic anemias
1. Increase in erythropoiesis and reticulocytosis.
2. Retention of iron .
3. In severe cases, extramedullary hematopoesis often develop in
spleen, liver, and lymph nodes.
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Intravascular versus extravascular hemolysis.
INTRAVASCULAR HEMOLYSIS
Causes of intravascular hemolysis :
1. Trauma (defective heart valve)
2. Biochemical or physical agents that damage the red cell
membranes
Intravascular hemolysis leads to:
a. Hemoglobinemia & Hemoglobinuria.
b. Hemosiderinuria .
c. Conversion of the heme pigment to bilirubin can result in
jaundice.
d. Renal acute tubular necrosis.
EXTRAVASCULAR HEMOLYSIS
- Is more common than intravascular and takes place
within the macrophages of the spleen and liver.
- Because extreme alterations of shape are necessary for
red cells to successfully navigate the splenic sinusoids,
any reduction in red cell deformability makes this
passage difficult and leads to splenic sequestration,
followed by phagocytosis.
Extravascular hemolysis :
a. No hemoglobinemia or hemoglobinuria .
b. Produces jaundice and pigmented gallstones.
c. There is splenomegaly .
d. In chronic forms, iron accumulates, giving rise to
systemic hemosiderosis .
I. HEREDITATORY
SPHEROCYTOSIS
(HS)
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Characterized by an inherited (Intrinsic) defect in red cell
membrane that makes the cell spheroidal, less deformable,
and vulnerable to splenic destruction.
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Because of limited deformability, spherocytes are destroyed by
macrophages of spleen and the role of the spleen is illustrated
by the beneficial effect of splenectomy and although the
spherocytes persist, the anemia is corrected .
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The characteristic clinical features are anemia,
splenomegaly and jaundice .
II. SICKLE CELL ANEMIAS
The hemoglobinopathies are a group of hereditary
disorders that are defined by the presence of
structurally abnormal hemoglobins.
The most common hemoglobinopathy is caused by mutation in
the B-globin chain gene that creates sickle hemoglobin (HbS)
Upon deoxygenation , HbS molecules undergo polymerization,
and these polymers distort the red cell, which assumes a
crescentic , or sickle in shape .
- Sickling of red cells is initially reversible upon reoxygenation.
However, membrane damage occurs with each episode of
sickling, and eventually the cells become irreversibly sickled .
VARIABLES INFLUENCE SICKLING OF RED CELLS
a.
The presence of hemoglobins other than HbS. The presence
of HbA and HbF slows the rate of polymerization greatly.
That’s why sickle cell disease usually becomes apparent
after the sixth month of life.
b.
The concentration of HbS in the cell. red cell dehydration,
which increases the Hb concentration, greatly facilitates
sickling and can trigger occlusion of small blood vessels
c.
The length of time that red cells are exposed to low oxygen
tension. sickling is confined to microvascular beds where
blood flow is sluggish. This is normally the case in the
spleen and the bone marrow, which are prominently affected
by sickle cell disease.
d.
Inflammation and infection causes slowing of blood flow
and this enhance significant sickling.
TWO MAJOR CONSEQUENCES STEM FROM
THE SICKLING OF RED CELLS
1.
repeated episodes of deoxygenation cause membrane
damage and dehydration of red cells, which become
rigid and irreversibly sickled. producing a chronic
extravascular hemolytic anemia. Overall, the mean
life span of red cells in sickle cell anemia patients
averages only 20 days.
2.
widespread microvascular obstructions, which result
in ischemic tissue damage and pain crises. appears to
result from factors, such as infection, inflammation,
dehydration, and acidosis.
CLINICAL FEATURES:
1- Severe chronic hemolytic anemia
2- Increased breakdown of heme pigments, which are
processed into bilirubin with resultant jaundice
3- Microvascular obstruction, which provokes tissue
ischemia and infarction and can affect any organ.
4- extramedullary hematopoesis
5- prominent cheekbones and changes in the skull .
6- splenomegaly and autosplenectomy.
7- hemosiderosis and gallstones are common.
COMPLICATIONS
1- acute chest syndrome, which can be triggered by
pulmonary infections or fat emboli from necrotic marrow
that secondarily involve the lung.
2- central nervous system stroke,
3- Vaso-occlusive or pain crises, affects the bone marrow.
2. The aplastic crisis is a sudden but temporary cessation
of erythropoiesis, triggered by parvovirus B19 infection
of erythroblasts.
III. THALASSEMIAS
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A group of inherited disorders caused by mutations that
decrease the rate of synthesis of alpha or beta -globin
chains and as a consequence there is a deficiency of
hemoglobin, with secondary red cell abnormalities
caused by relative excess of the other unaffected globin
chain.
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Adult hemoglobin, or HbA, is a tetramer composed of
two α chains and two β chains
B-THALASSEMIA:
types of mutations
a. B0 : no B-globin chains are produced
b. B+: reduced but detectable B-globin synthesis:
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Thalassemia major: both chains mutated.
Thalassemia minor or thalassemia trait, only one
mutation, which is asymptomatic microcytic anemia or
mild microcytosis without anemia .
Unpaired alpha chains form aggregates that precipitate
within the red cells , causing severe membrane
damage to provoke extravascular hemolysis .
Microcytic hypochromic anemia.
Clinical course:
B-thalassemia major manifests itself postnatally as HbF
synthesis is decreased and affected children fail to develop
normally, with growth retardation shortly after birth.
Skeletal deformities, splenomegaly, hepatomegaly,
cachexia.
- They are sustained only by repeated blood transfusions,
which improve the anemia and reduce the skeletal
deformities
- With transfusion alone survival into the-- second or third
decade is possible.
- Hemochromatosis results from iron overload from
transfused red cells and unless the patients are treated with
iron chelators , cardiac failure causes death in the second or
third decade of life
IV. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY
The red cells are vulnerable to injury by oxidants and
free radicals, which are normally inactivated by the
reduced form of glutathione (GSH)
 Abnormalities affecting the enzymes required for
GSH production reduce the ability of red cells to be
protected from oxidative injury, lead to hemolytic
anemias.
 Regeneration of GSH is impaired in G6PD-deficient
cells
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It is an x-linked recessive disorder.
Intravascular and extravascular hemolysis.
It produces no symptoms until the patient is exposed to an
environmental factor mostly infections and drugs (antimalarial
primaquine and sulfonamides), that results in oxidant stress.
Also might be triggered by oxidants in certain foods like Fava
beans.
3-ANEMIAS OF DIMINISHED
ERYTHROPOIESIS
A- Iron Deficiency Anemia:
Is the most common form of anemia of nutritional
deficiency.
Normally, serum iron levels is 120 μg/dL in men and 100
μg/dL in women.
Causes:
1. In non developed countries, low intake and vegetarian
diets are an important cause of iron deficiency
2. Malabsorption such as celiac disease.
3. Increased demands during pregnancy and infancy.
4. Chronic blood loss is the most important cause of iron
deficiency anemia in the western world and it may
occur from , peptic ulcers, intestinal ulcers, colonic
cancer, hemorrhoids) or the female genital tract (e.g.,
menstruation, cancers).
CLINICAL COURSE
a. In most instances ,it is asymptomatic.
b. Nonspecific manifestations, such as weakness,
listlessness, and pallor,
c. With severe anemia, flattening, and "spooning" of the
fingernails appears.
d. A curious neuro-behavioral complication is pica, the
tendency to consume non-foodstuffs such as dirt or clay.
e. Anemia is microcytic hypochromic.
 impaired work and cognitive performance
 No extramedullary hematopoesis.
B- Folate (Folic Acid) Deficiency Anemia
Megaloblastic anemia secondary to folate deficiency is not
common .
The risk of clinically significant folate deficiency is high
with poor diet or increased needs (pregnant women).
Folate is widely prevalent in nearly all foods but is readily
destroyed by 10 to 15 minutes of cooking. so the best
sources of are fresh uncooked vegetables and fruits.
Causes of folate deficiency anemia:
a. Decreased absorption by acidic foods and substances found
in beans
b. Phenytoin (Dilantin) inhibit absorption and methotrexate inhibit
metabolism.
c. The site of intestinal absorption is the small intestine; thus,
malabsorptive disorders such as celiac disease and
tropical sprue, can impair folate uptake .
Clinical features:
- Weakness and easy fatigability.
- sore tongue and cheilosis
- It should be stressed that, unlike in vitamin B12 deficiency,
neurologic abnormalities do not occur
C . Vitamin B12 Deficiency:
long-standing malabsorption is the most common and important
cause.
- Vitamin B12 is abundant in all animal foods, including eggs and
dairy products, and is resistant to cooking and boiling..
- As a result, deficiencies due to diet are rare and are virtually
confined to strict vegeterians because vit B12 is stored in the
liver, which normally contains reserves that are sufficient to
support bodily needs for 5 to 20 years.
Until proved otherwise, a deficiency of vitamin B12 (in the
western world) is caused by pernicious anemia and this
disease seems to stem from an autoimmune reaction against
parietal cells and intrinsic factor itself, which produces gastric
mucosal atrophy .
 Chronic vitamin B12 malabsorption is seen following
gastrectomy or resection of ileum and in disorders that
involve the distal ileum (Crohn disease)
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Clinical Features
1. Pallor, easy fatigability, and, in severe cases, dyspnea and
heart failure.
2. The principal neurologic lesions associated with vitamin B12
deficiency are symmetric numbness, tingling, and burning in
feet or hands, followed by unsteadiness of gait .
Although the anemia responds dramatically to parenteral vitamin
B12, the neurologic manifestations often fail to resolve
Uncommonly, the neurologic disease occurs in the absence of
overt anemia
D- APLASTIC ANEMIA
- Characterized by marrow failure and pancytopenia
Etiology and Pathogenesis
a. In more than ½ of cases, it is idiopathic.
b. In the remainder, an exposure to drugs or chemicals, such as
chloramphenicol
c. certain viral infections, most often community-acquired viral
hepatitis,
Slowly progressive anemia causes the insidious
development of weakness, pallor, and dyspnea.
 Thrombocytopenia often presents with petechiae and
ecchymoses.
 Granulocytopenia may be manifested only by frequent
and persistent minor infections or by the sudden onset of
chills and fever.
 Splenomegaly is characteristically absent.
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THROMBOCYTOPENIA :
Thrombocytopenia is characterized by
spontaneous bleeding, a prolonged bleeding
time, and a normal PT and PTT
- A platelet count of 100000 cells/µL considered to constitute
thrombocytopenia
- Platelet count in the range of 20,000 to 50,000 cells/µL are
associated with an increased risk of post-traumatic bleeding,
- Spontaneous bleeding becomes evident - when count falls
below 20,000 cells/µL
CLINICAL FEATURES:
- Most bleeding tends to occur from superficial blood
vessels and produce petechiae or large ecchymosis in the
skin, the mucous membranes of gastrointestinal and
urinary tracts.
- Larger hemorrhages into the central nervous system are a
major hazard in patients with markedly decreased
platelet counts
IMMUNE THROMBOCYTOPENIC PURPURA (ITP)
- Called idiopathic thrombocytopenic purpura
- It can be Primary or idiopathic (in the absence of any
known risk factors) or Secondary .
- There are two main types of primary ITP
1. Chronic primary ITP: A common disorder that tends
to affect adult females between ages of 20 and 40
years
2. Acute primary ITP: A self-limited form that is most
commonly seen in children due to viral infections
The spleen is usually normal in size and thus splenic
enlargement or lymphadenopathy should lead
one to consider other possible diagnoses
The importance of the spleen in this disorder is confirmed
by the clinical benefits produced by splenectomy,
- The bone marrow usually contains increased numbers of
megakaryocytes, a finding common to all forms of
thrombocytopenia caused by accelerated platelet
destruction
- A marrow examination is helpful in excluding marrow
failure