Essentials of Pathophysiology
CHAPTER 13
THE RED BLOOD CELL AND ALTERATIONS
IN OXYGEN TRANSPORT
PRE LECTURE QUIZ (TRUE/FALSE)
T

F

F
F

F


There are two major types of hemoglobin—adult
hemoglobin (HbA) and fetal hemoglobin (HbF).
Sickle cell disease is a chronic disorder that results from
changes in the size of red blood cells, not their shape.
Iron-deficiency anemia affects only infants and toddlers.
Hyperbilirubinemia is an increased level of serum bilirubin
and very often causes cyanosis in the neonate.
Thalassemias are inherited disorders of platelet synthesis
that cause severe bruising and bleeding.
PRE LECTURE QUIZ
Aplastic
Erythrocytes

Mature red blood cells are also known as
____________________.

The function of red blood cells is to transport
____________________ from the lungs to the tissues.

If red blood cell destruction is excessive, bilirubin
production is increased, causing a yellow discoloration of
the skin called ______________________.

Rh disease of the newborn is an example of
____________________ anemia.

____________________ anemia describes a primary
condition of bone marrow stem cells that results in a
reduction of all three hematopoietic cell lines—red blood
cells, white blood cells, and platelets.
Hemolytic
Jaundice
oxygen
ADULT HEMOGLOBIN




Two alpha chains
Two beta chains
Each protein chain holds
one iron-containing heme
group
Oxygen binds to the heme
groups
QUESTION
How many molecules of oxygen can be carried by
one molecule of hemoglobin?
a. 1
b. 2
c. 3
d. 4
ANSWER
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.
ERYTHROPOIESIS
• Why would a man
receiving chemotherapy
for cancer develop
anemia?
decreased blood
oxygen
• Why would a man with
renal failure develop
anemia?
kidneys secrete
erythropoietin
bone
marrow
stimulated
creates new
red blood cells
RED BLOOD CELLS
bone marrow creates
new red blood cells:
may release
immature
RBCs
(nucleated)
reticulocytes (RBCs
that still have their
endoplasmic reticulum)
mature
RBCs
RBCS LAST ABOUT 120 DAYS



Their membranes become
weakened
Because they have no nuclei,
RBCs cannot make new
membrane components, Why?
Eventually, RBCs break as
they squeeze through the
capillaries
mature
RBCs
circulate
for 120
days
become
damaged
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?
Answer: Spleen & Liver have sluggish
circulation subject to clotting
causing ischemia with lack of
circulation to carry away toxins
break in
capillaries
of the
spleen
eaten by white blood
cells in the spleen, liver,
bone marrow, or lymph
nodes
hemoglobin
processed
into
bilirubin
THE FATE OF BILIRUBIN

Unconjugated bilirubin is
toxic
Question:
 Why would a man
with liver failure
develop jaundice?
unconjugated
bilirubin in
blood
X
bilirubinemia liver links it
to
gluconuride
jaundice
conjugated
bilirubin
bile
MALARIA PARASITES
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
QUESTION
Red blood cells (erythrocytes) are made in the
________ and destroyed in the _________.
a.
b.
c.
d.
kidneys, liver
kidneys, spleen
bone marrow, spleen
bone marrow, liver
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.
CAUSES OF ANEMIA
Blood loss
 Hemolysis
 Impaired RBC
production

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?
ANEMIAS OF DEFICIENT RBC PRODUCTION
Iron deficiency anemia (often caused by blood
loss)
 Megaloblastic anemias

 Cobalamin
(Vitamin B12) deficiency (Needed for
DNA replication)
º
Pernicious anemia
 Folic
acid deficiency (Needed for DNA replication)
Aplastic anemia (bone marrow depression)
 Chronic disease anemias

 Chronic
inflammation
 Lymphocyte
production
 Chronic
cytokines suppress erythropoietin
renal failure
 Erythropoietin
not produced
IRON-DEFICIENCY ANEMIA
 Hypochromic
and
microcytic erythrocytes
 Poikilocytosis (irregular
shape) (poi'kə-lō-sī-tō'sĭs)
 Anisocytosis (irregular
size) (ān-ī'sō-sī-tō'sĭs)
(Rubin E., Farber J.L. [1999]. Pathology [3rd
ed., p. 1077]. Philadelphia: Lippincott-Raven.)
VITAMIN B12 DEFICIENCY (PERNICIOUS ANEMIA)
Megaloblastic anemia
 Erythrocytes are large,
often with oval shape
 Poikilocytosis and
teardrop shapes
 Anisocytosis (Irreg. size)
 Neutrophils are
hypersegmented

(Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 1076]. Philadelphia: LippincottRaven.)
SCENARIO
A boy presents with:
 Pallor
 Weakness
 Low red blood cell count
 Increased respiratory and heart rates
 Yellow skin
 Dark brown urine
 Enlarged spleen and liver
Question:
 What is your diagnosis?
 Is he lacking RBC production or hemolytic anemia?
 Which symptoms are caused by decreased RBC count?
 By GAS?
 By hemolysis?
QUESTION
Which type of deficiency causes pernicious
anemia?
a. Iron
b. Vitamin B6
c. Vitamin B12
d. Folic acid
ANSWER
c.
Vitamin B12
Rationale: Intrinsic factor produced by cells of the
gastric mucosa binds vitamin B12 and assists
absorption of B12. When gastric mucosa cells
are lacking often due to autoimmune
antibodies attacking gastric mucosa
production of IF is reduced and B12 is not
absorbed.
HEMOLYTIC ANEMIAS



Membrane disorders , RBC shape and fragility
 Hereditary spherocytosis (shape holding inner membrane)
 Acquired hemolytic anemias (chemicals drugs, antibodies)
hemolytic disease of the newborn-Rh incompatibility
any of a group of inherited hypochromic anemias
Hemoglobinopathies
and especially Cooley's anemia controlled by a
series of allelic genes that cause reduction in or
 Sickle cell disease
failure of synthesis of one of the globin chains
making up hemoglobin and that tend to occur
 Thalassemia
especially in individuals of Mediterranean, African, or
southeastern Asian ancestry —sometimes used with
º Alpha
a prefix (as alpha-, beta-, or delta-) to indicate the
hemoglobin chain affected.
º Beta
G6PD deficiency (Glucose 6 Phosphate Dehydrogenase
enzyme deficiency- limits RBC’s ATP production)
G6PD

G6PD Easily mistaken for malaria.
 Heinz
bodies on the periphery
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”
SICKLE CELL DISEASE

Mutation in beta chains of hemoglobin

At a single location in the protein chain valine is substituted for
glutamic acid
Valine
Glutamic acid

When hemoglobin is deoxygenated, beta chains link
together, forming long protein rods that make the cell
“sickle”
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 (Pneumonia)
 Cerebral infarction  stroke
Sickled cells more likely to be destroyed
 Releasing excess bilirubin
Jaundice
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’s population will have sickle trait?
Use the Hardy-Wienberg Equilibrum equations:
p+q=1 ; p= probability of normal gene and q = prob. of Sickle
q2 + 2pq + p2 =1 ; 2pq= freq of occurrence of father’s
genotype, heterozygous



SICKLE CELL DISEASE INHERITANCE
s = Sickle Gene
 S= nonSickle
 percentage of their children

s
s
S
Ss
Ss
s
ss
ss
Father has
the Trait, Ss
Mother has the disease, ss
Possible Children’s Genotype
50% have the disease, ss
50% are Heterozygous, Ss
SOLVE FOR FREQUENCY HETEROZYGOTES IN
THE POPULATION







Use the Hardy-Wienberg Equilibrum equations:
p+q=1 ; p= probability of normal gene and q = prob. of
Sickle
q2 + 2pq + p2 =1 ; 2pq= freq of occurrence of father’s
genotype, heterozygous
Given: Frequency of Sickle gene = 10%
In the Hardy-Wienberg equation q=.1
Therefore p= 1-.1=.9 or 90% of genes are normal
q2 = percent with sickle disease = (.1)2 = .01 =1%
Question: What is the % heterozygous
From equations 2pq= 2(.1*.9) =.18 or 18% have the
trait without the disease
QUESTION
True or False.
Patients with sickle cell disease who also suffer
from lung diseases are more prone to sickling.
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.
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
Some treatments
include inducing HbF
production
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
SCENARIO
A woman has β thalassemia. p219
 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(Thin cortical bone w/ enlarged marrow. Bone deposition
on jaw)
 She has Heinz bodies (precipitate aggregate of excess α chains
in RBC)
 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?