Chapter 13
Disorders of Red Blood Cells
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Adult Hemoglobin
• Two alpha chains
• Two beta chains
• Each protein chain holds one iron-containing heme
group
• Oxygen binds to the heme groups
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Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
How many molecules of oxygen can be carried by one
molecule of hemoglobin?
a. 1
b. 2
c. 3
d. 4
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Answer
d. 4
Each hemoglobin molecule has 2 alpha and 2 beta protein
chains. Each chain contains 1 heme group. Each heme
group (4 chains = 4 heme groups) is capable of carrying
1 molecule of oxygen.
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Erythropoiesis
• Why would a man
receiving chemotherapy
for cancer develop
anemia?
• Why would a man with
renal failure develop
anemia?
decreased blood
oxygen
kidneys secrete
erythropoietin
bone
marrow
stimulated
creates new
red blood cells
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Red Blood Cells
bone marrow creates
new red blood cells:
may release
immature
RBCs
(nucleated)
reticulocytes (RBCs
that still have their
endoplasmic reticulum)
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mature
RBCs
mature
RBCs
RBCs Last about 120 Days
• Their membranes
become weakened
• Because they have no
nuclei, RBCs cannot
make new membrane
components
• Eventually, RBCs break
as they squeeze through
the capillaries
circulate
for 120
days
become
damaged
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Most RBCs Break
in the Spleen
• White blood cells living in
the spleen are ready to
process RBCs
• Creating unconjugated
bilirubin
Question:
• Why would a man
with defective red blood
cells develop
hepatosplenomegaly?
break in
capillaries
in the
spleen
eaten by white blood
cells in the spleen, liver,
bone marrow, or lymph
nodes
hemoglobin
processed
into
bilirubin
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The Fate of Bilirubin
• Unconjugated
bilirubin is toxic
Question:
• Why would a man with
liver failure develop
jaundice?
unconjugated
bilirubin in
blood
bilirubinemia liver links it
to
gluconuride
jaundice
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conjugated
bilirubin
bile
When RBCs Are Destroyed
Outside the Spleen …
• Hemoglobinemia
makes the plasma
turn red
• Hemoglobinuria
makes the urine
cola-colored
break in
capillaries outside
the spleen
hemoglobin
released into the
blood
Question:
• Why was malaria
called “blackwater
fever?”
hemoglobinemia
hemoglobinuria
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Question
Red blood cells (erythrocytes) are made in the ________
and destroyed in the _________.
a. kidneys, liver
b. kidneys, spleen
c. bone marrow, spleen
d. bone marrow, liver
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Answer
c. bone marrow, spleen
Erythropoietin, made in the kidneys, stimulates the bone
marrow to produce RBCs. Eventually, RBCs break up in
the capillaries of the spleen and their hemoglobin is
processed as bilirubin in the liver.
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Causes of Anemia
• Blood loss
• Hemolysis
• Impaired RBC production
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Scenario:
A man had severe anemia and developed…
• Weakness
•
Angina
•
Fainting
•
Tachycardia
•
Sweating and pallor
•
Pain in his bones and sternum
Question:
• Which are caused by decreased RBCs, O2? By compensation using
the GAS? By attempts to replace the RBCs?
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Anemias of Deficient RBC Production
• Iron-deficiency anemia (often caused by blood loss)
• Megaloblastic anemias
– Cobalamin (vitamin B12) deficiency
º Pernicious anemia
– Folic acid deficiency
• Aplastic anemia (bone marrow depression)
• Chronic disease anemias
– Chronic inflammation
– Chronic renal failure
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Iron-Deficiency Anemia
• Hypochromic and
microcytic
erythrocytes
• Poikilocytosis
(irregular shape)
• Anisocytosis
(irregular size)
(Rubin E., Farber J.L. [1999]. Pathology [3rd
ed., p. 1077]. Philadelphia: Lippincott-Raven.)
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Vitamin B12 Deficiency (Pernicious
Anemia)
• Megaloblastic anemia
• Erythrocytes are
large, often with oval
shape
• Poikilocytosis and
teardrop shapes
• Neutrophils are
hypersegmented
(Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 1076]. Philadelphia: LippincottRaven)
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Scenario:
A
•
•
•
•
•
•
•
boy presents with …
Pallor
Weakness
Increased respiratory and heart rate
Enlarged spleen and liver
Yellow skin
Dark brown urine
Low red blood cell count
Question:
• Does he have a deficiency or hemolytic anemia?
Which symptoms are caused by decreased RBC
count and hypoxia? By GAS? By hemolysis?
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Question
Which type of deficiency is caused by pernicious anemia?
a. Iron
b. Vitamin B6
c. Vitamin B12
d. Folic acid
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Answer
c. Vitamin B12
Pernicious anemia destroys the gastric mucosa, producing
antibodies that block the binding of vitamin B12 to the
intrinsic factor, blocking its absorption into the
bloodstream.
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Hemolytic Anemias
• Membrane disorders
– Hereditary spherocytosis
– Acquired hemolytic anemias and
hemolytic disease of the newborn
• Hemoglobinopathies
– Sickle cell disease
– Thalassemia
º Alpha
º Beta
• G6PD deficiency
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Sickle Cell Disease
• Mutation in beta chains
of hemoglobin
• When hemoglobin is
deoxygenated, beta
chains link together 
Forming long protein
rods that make the cell
“sickle”
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Problems Caused by Sickle Cell
• Sickled cells block capillaries
– Acute pain
– Infarctions cause chronic damage to liver,
spleen, heart, kidneys, eyes, bones
– Pulmonary infarction  acute chest syndrome
– Cerebral infarction  stroke
• Sickled cells more likely to be destroyed
– Jaundice
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Sickle Cell Anemia Inheritance
Scenario:
• A man has sickle trait (heterozygous for sickle cell)
• His wife has sickle cell disease
Question:
• What percentage of their children will have the disease?
• In a population, the gene frequency of the sickle cell allele is
10%
• Assuming the gene is equally common in males and females
and does not affect reproduction, what percentage of the next
generation will have sickle trait?
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Question
Tell whether the following statement is true or false:
Patients with sickle cell anemia who also suffer from lung
diseases are more prone to sickling.
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Answer
True
Hypoxia, which is more likely to occur in lung/pulmonary
disease, is an important exacerbating factor associated
with increased sickling and vessel occlusion.
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Fetal Hemoglobin Has No Beta Chains
• It has alpha chains and gamma chains
• This means it cannot sickle
• Persons with some fetal hemoglobin are partially
protected from sickle cell disease
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Thalassemias
Alpha
Beta
• Defective gene for alphachain synthesis
• Defective gene for betachain synthesis
• May have 1–4 defective
genes
• May have 1–2 defective
genes
• Affects both fetal and
adult Hb
• Affects only adult Hb
• In fetus, gamma4 Hb may
form; in adult, beta4 Hb
may form
• Alpha4 Hb may form
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Scenario:
A woman has thalassemia …
• She has pale skin and gums, fatigue, and headaches
• She has been treated with transfusions since childhood
• Her jaw is enlarged; she has had two leg fractures in the
past year
• She has Heinz bodies
• Her liver is enlarged; she has jaundice and liver failure
Question:
• Which of these signs and symptoms are due to anemia,
which to compensatory erythropoiesis, and which to
treatment?
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