1. Chapter 13 The Red Blood Cell and Alterations in Oxygen Transport
Essentials of Pathophysiology
Chapter 13 The Red Blood Cell and Alterations in Oxygen Transport

2. 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.

3. 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

4. Adult Hemoglobin Two alpha chains Two beta chains
Each protein chain holds one iron-containing heme group
Oxygen binds to the heme groups

5. Question
How many molecules of oxygen can be carried by one molecule of hemoglobin? 1 2 3 4

6. 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.

7. 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

8. Red Blood Cells bone marrow creates new red blood cells: may release
immature
mature
reticulocytes (RBCs
RBCs
RBCs
that still have their
(nucleated)
endoplasmic reticulum)

9. mature RBCs circulate for 120 days become damaged
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

10. Most RBCs Break in the Spleen
capillaries
of the
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
spleen
eaten by white blood
cells in the spleen, liver,
bone marrow, or lymph
nodes
hemoglobin
processed
into
bilirubin

11. Why would a man with liver failure develop jaundice?
unconjugated
The Fate of Bilirubin
bilirubin in
blood X
Unconjugated bilirubin is toxic
Question:
Why would a man with liver failure develop jaundice?
bilirubinemia
liver links it to
gluconuride
jaundice
conjugated
bilirubin
bile

12. Malaria parasites

13. When RBCs Are Destroyed Outside the Spleen…
break in
capillaries outside
the spleen
Hemoglobinemia makes the plasma turn red
Hemoglobinuria makes the urine cola-colored
Question:
Why was malaria called “blackwater fever?”
hemoglobin
released into the
blood
hemoglobinemia
hemoglobinuria

14. Question
Red blood cells (erythrocytes) are made in the ________ and destroyed in the _________.
kidneys, liver
kidneys, spleen
bone marrow, spleen
bone marrow, liver

15. Answer
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.

16. Author: Please add title.

17. Causes of Anemia
Blood loss
Hemolysis
Impaired RBC production

18. Question: 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?

19. 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

20. 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.)

21. 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.)

22. 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?

23. Question
Which type of deficiency causes pernicious anemia?
Iron
Vitamin B6
Vitamin B12
Folic acid

24. Answer
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.

25. 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
Alpha
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.

26. G6PD
G6PD Easily mistaken for malaria.
Heinz bodies on the periphery

27. 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”

28. 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

29. 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

30. 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

31. Possible Children’s Genotype
Sickle Cell Disease Inheritance
s = Sickle Gene
S= nonSickle
percentage of their children
Mother
s s
Father
Mother has the disease, ss S s Ss ss Ss ss
Possible Children’s Genotype
50% have the disease, ss
50% are Heterozygous, Ss
Father has the Trait, Ss

32. 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

33. Question
True or False. Patients with sickle cell disease who also suffer from lung diseases are more prone to sickling.

34. 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.

35. 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

36. 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

37. 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?