chapter 13 the red blood cell and alterations in oxygen transport essentials of pathophysiology
TRANSCRIPT
CHAPTER 13
THE RED BLOOD CELL AND ALTERATIONS IN OXYGEN TRANSPORT
Essentials of Pathophysiology
PRE LECTURE QUIZ (TRUE/FALSE)
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.
T
F
FF
F
PRE LECTURE QUIZ 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.
Aplastic
Erythrocytes
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. 1b. 2c. 3d. 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?
• Why would a man with renal failure develop anemia?
decreased blood oxygen
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
bilirubinemia
jaundice
liver links it to
gluconuride
conjugated bilirubin
bile
X
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. kidneys, liverb. kidneys, spleenc. bone marrow, spleend. 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 cytokines suppress erythropoietin
production Chronic 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: Lippincott-Raven.)
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. Ironb. 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
Hemoglobinopathies Sickle cell disease Thalassemia
º Alpha º Beta
G6PD deficiency (Glucose 6 Phosphate Dehydrogenase enzyme deficiency- limits RBC’s ATP production)
any of a group of inherited hypochromic anemias and especially Cooley's anemia controlled by a 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
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
When hemoglobin is deoxygenated, beta chains link together, forming long protein rods that make the cell “sickle”
Valine
Glutamic acid
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
s = Sickle Gene S= nonSickle percentage of their children
SICKLE CELL DISEASE INHERITANCE
Father
Mother
S
s
Ss
ss
Ss
ss
s s
50% have the disease, ss50% are Heterozygous, Ss
Mother has the disease, ss
Father has the Trait, Ss
Possible Children’s Genotype
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
TrueRationale: 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 alpha-
chain synthesis
• May have 1–4 defective genes
• Affects both fetal and adult Hb
• In fetus, gamma4 Hb may form; in adult, beta4 Hb may form
• Defective gene for beta-chain synthesis
• May have 1–2 defective genes
• Affects only adult Hb
• 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?