1. Chapter 11 The Red Blood Cell and Alterations in Oxygen Transport

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

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

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.

5. decreased blood
Erythropoiesis
oxygen
Why would a man receiving chemotherapy for cancer develop anemia?
Why would a man with renal failure develop anemia?
kidneys secrete
erythropoietin
bone
marrow
stimulated
creates new
red blood cells

6. 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)

7. 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
Eventually, RBCs break as they squeeze through the capillaries
circulate
for 120
days
become
damaged

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

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

10. When RBCs Are Destroyed Outside the Spleen…
break in
When RBCs Are Destroyed Outside the Spleen…
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

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

12. 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.

13. Causes of Anemia
Blood loss
Hemolysis
Impaired RBC production

14. 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?

15. Anemias of Deficient RBC Production
Iron deficiency anemia (often caused by blood loss)
Megaloblastic anemias
Cobalamin (Vitamin B12) deficiency
Pernicious anemia
Folic acid deficiency
Aplastic anemia (bone marrow depression)
Chronic disease anemias
Chronic inflammation
Chronic renal failure

16. 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.)

17. 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: Lippincott-Raven.)

18. 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?

19. Question Which type of deficiency is caused by pernicious anemia? Iron
Vitamin B6
Vitamin B12
Folic acid

20. Answer
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.

21. Hemolytic Anemias Membrane disorders Hereditary spherocytosis
Acquired hemolytic anemias and hemolytic disease of the newborn
Hemoglobinopathies
Sickle cell disease
Thalassemia
Alpha
Beta
G6PD deficiency

22. 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”

23. 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

24. 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?

25. 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.

26. 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.

27. 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

28. 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

29. 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?