Essentials of Pathophysiology

CHAPTER 13
THE RED BLOOD CELL AND
ALTERATIONS IN OXYGEN
TRANSPORT

PRE LECTURE QUIZ

T

F
F

(TRUE/FALSE)

There are two major types of hemoglobinadult

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

Hemolytic
Jaundice

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 linesred blood cells, white

oxygen

ADULT HEMOGLOBIN

Two alpha chains

Two beta chains
Each protein chain
holds one ironcontaining 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

mature
RBCS LAST ABOUT 120 DAYS
RBCs

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

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
hepatosplenomegal
y?

Answer: Spleen & Liver have

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)

Pernicious anemia

Folic acid deficiency (Needed for DNA replication)

Aplastic anemia (bone marrow depression)

Chronic disease anemias

Chronic inflammation

Lymphocyte cytokines suppress erythropoietin

production

Chronic renal failure

Erythropoietin not produced

IRON-DEFICIENCY ANEMIA

Hypochromic and
microcytic
erythrocytes
Poikilocytosis
(irregular shape)
(poi'k-l-s-t'ss)

Anisocytosis
(irregular size) (n's-s-t'ss)

(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 B 12 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 B 12
is not absorbed.

HEMOLYTIC ANEMIAS

Membrane disorders , RBC shape and fragility

Hereditary spherocytosis (shape holding inner

membrane)

Acquired hemolytic anemias (chemicals drugs,

antibodies)
any of a group of inherited hypochromic anemias
hemolytic disease of the
incompatibility
andnewborn-Rh
especially Cooley's
anemia controlled by a

Hemoglobinopathies

Sickle cell disease

Thalassemia

Alpha

Beta

series of allelic genes that cause reduction in or

failure of synthesis of one of the globin chains
making up hemoglobin and that tend to occur
especially in individuals of Mediterranean, African, or
southeastern Asian ancestry sometimes used with
a prefix (as alpha-, beta-, or delta-) to indicate the
hemoglobin chain affected.

G6PD deficiency (Glucose 6 Phosphate Dehydrogenase

enzyme deficiency- limits RBCs 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 generations 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 fathers
genotype, heterozygous

SICKLE CELL DISEASE INHERITANCE

s = Sickle Gene
S= nonSickle
percentage
of
their
children
M
o
Fa the
the r
r

s s

Mother has the disease, ss

Ss

Ss

ss

ss

Father has
the Trait, Ss

Possible Childrens 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 fathers 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%

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 14 defective

genes

May have 12 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 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 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?