(17.3) RBCs

List the Composition of Formed Elements

1. RBCs

2. WBCs

3. Platelets

Describe the Formed Elements

• Only WBCs are complete cells

• Most formed elements survive in bloodstream “only few days”

• Most blood cells originate in bone marrow and do not divide

Describe the Structure of Erythrocytes

• Small-diameter (7.5 um) cells that contribute to gas transport

• Filled with hemoglobin (Hb) for gas transport

What is a hematocrit?

• A hematocrit is the percentage of erythrocytes in a whole blood sample

• 45% of whole blood (Hct) 

How to calculate Hematocrit

• HCT (%) = (RBCs/Whole Blood) x 100

• 40–54% for men and 36–48% for women

Explain how RBCs an superb example of Complementarity of Structure and Function 

• Three features make for efficient gas transport:

  1. Biconcave shape → offers huge surface area relative to volume for gas exchange

  2. Hemoglobin → makes up 97% of cell volume (not counting water), the molecule that binds to and transport respiratory gases

  3. RBCs have no mitochondria → ATP production is anaerobic, so they do not consume O2 they transport

  4. Flexible proteins → allow the cell to bend, twist, and cup, but which will return it to its normal shape

RBCs Function

• Erythrocytes are completely dedicated to their job of transporting respiratory gases (oxygen and carbon dioxide)

  1. O₂ loading in lungs → Produces oxyhemoglobin (ruby red) 

  2. O₂ unloading in tissues → Produces deoxyhemoglobin, or reduced hemoglobin (dark red) 

  3. CO₂ loading in tissues → 20% of CO₂ in blood binds to Hb, producing carbaminohemoglobin

What is the name of the protein found in erythrocytes that transports respiratory gases and provides the red color?

Hemoglobin 

Describe the structure and function of Hemoglobin

• LOCATION 

  • An iron-containing protein located within red blood cells

• STRUCTURE 

  • Consists of globin (two alpha and two beta polypeptide chains) and four heme groups 

  • Iron-containing heme-pigment 

• FUNCTION 

  • Hemoglobin molecule can transport four molecules of oxygen because each iron atom can combine reversibly with one molecule of oxygen

  • Each RBC contain 250 million Hb molecules 

What is the complete hemoglobin molecule composed of?

1. Four globin polypeptides (2 alpha chains, 2 beta chains)

2. Four heme groups

3. Four Fe²⁺ ions

O₂ vs CO₂ binding to Hemogolbin

• O₂→ binds to the heme group in hemoglobin (Hb)

  • 4 oxygen molecules can be transported by one Hb molecule

• CO₂ → binds to the amino groups on the hemoglobin protein chains

  • 4 carbon dixoide molecules can be transported by one Hb molecule

RBCs Production

Hematopoiesis → formation of all blood cells 

1. Occur in red bone marrow 

   • In adult, found in axial skeleton, girdles, and proximal epiphyses of humerus and femur 

2. Hematopoietic stem cells (hemocytoblasts)

   • Stem cell that gives rise to all formed elements

   • Hormones and growth factors push cell toward specific pathway of blood cell development

   • Committed cells cannot change

Explain how Erythropoiesis occurs

• Hematopoietic stem cells (hemocytoblasts) → Stem cell that gives rise to all formed elements

  • Hormones and growth factors push cell toward specific pathway of blood cell development

  • Committed cells cannot change

• Erythropoietin (EPO) → Hormone that stimulates formation of RBCS

  • Always small amount of EPO in blood to maintain basal rate

  • Released by kidneys (some from liver) in response to hypoxia

Stages of Erythropoiesis

Erythropoiesis → process of formation of RBS that takes about 15 days

1. Hematopoietic stem cell 

   • Bone marrow cell that gives rise to all the formed elements of blood; hemocytoblas

2. Myeloid stem cell 

   • A stem cell that gives rise to erythrocytes, platelets, and a few types of leukocytes

3. Proerythroblast 

   • A committed cell that gives rise to a basophilic erythroblast in the process of erythropoiesis

4. Basophilic erythroblasts

   • A cell in the developmental pathway of erythropoiesis that contains large numbers of ribosomes and transforms into a polychromatic erythroblast

5. Polychromatic erythroblasts 

   • A cell in the developmental pathway of erythropoiesis that synthesizes hemoglobin, accumulates iron, and transforms into an orthochromatic erythroblast.

6. Orthochromatic erythroblasts 

   • A cell in the developmental pathway of erythropoiesis that ejects most of its organelles and loses its nucleus as it becomes a reticulocyte.

7. Reticulocyte 

   • Young erythrocyte, still contains a bit of reticulum

8. Erythrocyte 

Causes and Effect of too few RBCs

• Hypoxia

  • Too few RBCs

• SYMPTOMS: 

  • Cyanosis 

  • Difficulty breathing 

  • Tachycardia 

  • Unconsciousness 

Causes and Effect of too high RBCs

• Increased blood viscosity 

  • Too many RBCs

Balance between RBC production and destruction depends on: 

1. Hormonal controls 

   • Erythropoietin (EPO) 

2. Dietary requirements 

   • Nutrients

   • Two B-complex vitamins

   • Iron

Explain Regulation of Release of RBCs

• STIMULATED by Erythropoietin (EPO) in response to

  • Hypoxia → inadequate O2 delivery due to:

    1. Decreased RBC count

    2. Decreased amount of hemoglobin

    3. Decreased availability of O2

• INHIBITED by

  • Too many erythrocytes

  • High O2

Role of Erythropoietin (EPO) 

• Erythropoietin (EPO) → Hormone that stimulates red bone marrow for the formation of RBCS

  • Always small amount of EPO in blood to maintain basal rate

  • Released by kidneys (some from liver) in response to hypoxia

• EPO causes erythrocytes to mature faster

  • Testosterone enhances EPO production, resulting in higher RBC count

Erythropoietin (EPO) mechanism for regulating erythropoiesis

1. STIMULI: Hypoxia (inadequate O₂ delivery due to)

   • Decreased RBC count

   • Decreased amount of hemoglobin

   • Decreased availability of O₂

2. Kidney (and liver to a smaller extent) releases Erythropoietin

3. Erythropoietin stimulates red bone marrow

4. Enhanced erythropoiesis increases RBC count  

5. O₂-carring ability of blood rises 

Explain Artificial EPO and its Effects

• Use of EPO increases hematocrit → which allows athlete to increase stamina and performance

• CONSEQUENCE → EPO can increase hematocrit from 45% up to even 65% with dehydration concentrating blood even more

List and Explain Dietary Requirements for Erythropoiesis

1. Nutrients 

   • Amino acids, lipids, and carbohydrates 

2. Iron 

   • 65% of iron is found in hemoglobin, which rest in liver, spleen, and bone marrow 

   • Free iron ions are toxic so iron is bound with proteins: 

     • Stored in cells as ferritin and hemosiderin

     • Transported in blood bound to protein transferrin 

3. Two B-complex vitamins

   • Vitamin B12 and folic acid are necessary for DNA synthesis for rapidly dividing cells such as developing RBCs

Explain RBCs Destruction

• Life span 100-120 days 

• Old RBCs become fragile, and Hb begins to degenerate

• Macrophages in spleen engulf and breakdown dying RBCs 

Explain RBC breakdown

RBC breakdown → heme, iron, and globin are separated

• Hemoglobin

  1. Heme → Molecule, containing iron

     • Iron removed and recycle, stored as ferritn or hemosiderin

     • Bilirubin Formation

  2. Globin → Protein component

     • Broken down into amino acids, which are recycled for the synthesis of new proteins, including new red blood cells

Explain Steps of Bilirubin Formation

Heme group has its iron removed and recycled, while the remainder is converted to bilirubin

1. Heme group is degraded to bilirubin (a yellow pigment) that is released to the blood 

2. Binds to albumin for transport  

3. Bilirubin is picked u by the liver

4. Bilirubin is secreted into intestine in bile where it is metabolized to stercobin by bacteria 

5. Stercoblin is exreted in feces 

Explain causes and effects of Jaundice

• Hyperbilirubinemia

  • A yellow discoloration of the body tissue resulting from the accumulation of excess bilirubin

• CAUSES 

  • Liver damage 

  • Hemolytic anemia → Too many RBCs destoryed

Classification of  Erythrocyte Disorders 

1. Anemia 

2. Polycythemia 

Describe Anemia

• Blood has abnormally low O₂-carrying capacity that is too low to support normal metabolism 

• Sign of problem rather than disease itself 

• SYMPTOMS: 

  • Shivering

  • Difficulty breathing

  • Lethargy

List the causes of Anemia 

1. Blood loss 

   • Hemorrhagic anemia

2. Not enough RBCs produced 

   • Iron-deficiency anemia

3. Too many RBCs being destroyed 

Describe the causes and treatment of Acute Hemorrhagic Anemia vs Chronic Hemorrhagic Anemia 

Blood loss 

• Acute Hemorrhagic Anemia

  • CAUSE → Blood loss is rapid (as might follow a severe stab wound)

  • TREATMENT → Replacing the lost blood

• Chronic Hemorrhagic Anemia 

  • CAUSE → Slight but persistent blood loss (due to hemorrhoids or an undiagnosed bleeding ulcer)

  • TREATMENT → Once the primary problem is resolved, normal erythropoietic mechanisms replace the lost blood cells

Describe the causes and treatment of Iron-deficiency anemia 

Not enough RBCs produced 

• CAUSE → Not enough RBCs being produced, can be caused by hemorrhagic anemia, but also by low iron intake or impaired absorption

  • RBCs produced are called microcytes → small and pale because they cannot synthesize their normal complement of hemoglobin

• TREATMENT → increase iron intake in diet (for example, red meat, beans, and spinach) or through iron supplements

Describe the causes and treatment of Pernicious anemia 

Not enough RBCs produced 

• CAUSE → Autoimmune disease that destroys stomach mucosa that produces intrinsic factor 

  • Intrinsic factor needed to absorb B₁₂

  • B₁₂ is needed to help developing RBCs divide

  • Without B12 developing RBCs enlarge but cannot divide, resulting in large macrocytes

• TREATMENT → regular intramuscular injections of vitamin B12 or application of a B12-containing gel to the nasal lining once a week

Microcytes vs Macrocytes

• Microcytes:

  • RBCs produced under Iron-deficiency anemia conditions

  • Small and pale because they cannot synthesize their normal complement of hemoglobin

• Macrocytes:

  • RBCs produced under Pernicious anemia  conditions

  • Developing RBCs enlarge but cannot divide, resulting in large cells

Describe the causes and treatment of Renal anemia

Not enough RBCs produced 

• CAUSE → lack of EPO

  • Often accompanies renal disease

  • Kidneys cannot produce enough EPO

• TREATMENT → Synthetic EPO

Describe the causes and treatment of Aplastic anemia

Not enough RBCs produced 

• CAUSE → Destruction or inhibition of bone marrow (drugs, chemicals, radiation or viruses)

  • Usually cause is unknown

  • All formed element cell lines are affected → results in anemia and clotting & immunity defects

• TREATMENT → short term with transfusion, long term with transplanted stem cells

Describe the causes Hemolytic anemia 

Too many RBCs being destroyed 

• Premature lysis of RBCs

• CAUSES: 

  • Incompatible transfusions or infections 

  • Hemoglobin abnormalities → usually genetic disorders resulting in abnormal goblin (Sickle-cell anemia) 

Describe the causes and treatment of Sickle-cell Anemia 

Too many RBCs being destroyed 

• CAUSE → Misshaped RBCs rupture easily and block small vessels

  • Hemoglobin S (HbS), results from a change in just one of the 146 amino acids in a beta chain of the globin molecule

  • Results in poor O₂ delivery and pain 

  • Prevalent in African-Americans of the African malarial belt and their descendants 

  • Possible benefit → people with sickle cell do not contract malerai 

    • Kills 1 million/year 

• TREATMENT → acute crisis treated with transfusion 

Describe Polycythemia 

• Abnormal excess of RBC

• SYMPTOMS: 

  • Increases blood viscosity → sluggish blood flow

Describe the causes and treatment of Polycythemia vera 

• CAUSE → Bone marrow cancer leading to excess RBC 

  • Hematocrit may as high as 80%

• TREATMENT → therapeutic phlebotomy  

Describe the causes Secondary Polycythemia  

CAUSE → low O2 levels (high altitude) or increased EPO production

Explain Blood doping

• Polycythemia 

• Athletes remove, store, and reinfuse RBCs before an event to increase O2 levels for stamina

Describe how changing tonicity leads to changes in RBC shape