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Chapter 11
The Red Blood Cell and
Alterations in Oxygen Transport
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Adult Hemoglobin
• Two alpha chains
• Two beta chains
• Each protein chain
holds one ironcontaining heme
group
• Oxygen binds to the
heme groups
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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
Rationale: 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.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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
of 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
conjugated
bilirubin
bile
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When RBCs Are
Destroyed
Outside the Spleen…
• Hemoglobinemia makes
the plasma turn red
• Hemoglobinuria makes
the urine cola-colored
Question:
• Why was malaria called
“blackwater fever?”
break in
capillaries outside
the spleen
hemoglobin
released into the
blood
hemoglobinemia
hemoglobinuria
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
c. bone marrow, spleen
Rationale: 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.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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 symptoms are caused by decreased RBCs, O2? By
compensation using the GAS? By attempts to replace the RBCs?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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.)
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
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.)
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Scenario
A
•
•
•
•
•
•
•
boy presents with:
Pallor
Weakness
Increased respiratory and heart rates
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
Rationale: 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 Disease
• 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 Disease 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 disease who also suffer from lung
diseases are more prone to sickling.
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Answer
True
Rationale: 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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