Chapter 21 - Blood Cells and the Hematopoietic System Notes

Chapter 21—Blood Cells and the Hematopoietic System

• Objectives:
  • Describe the composition and functions of plasma.
  • Describe the formed elements of blood and cite their function and life span.
  • Trace the process of hematopoiesis from stem cell to mature blood cell.
  • Describe the components of a complete blood count with differential.
  • Describe the various diagnostic tests used in determining laboratory values for RBCs, WBCs, and platelets.

Case Study: Charlie and Non-Hodgkin Lymphoma

• Charlie is a 53-year-old man with non-Hodgkin lymphoma.
• Treatment has been modestly successful but he has relapsed.
• Aggressive chemotherapy was decided upon.
• Stem cells were removed from his blood before chemotherapy to protect bone marrow.
• After chemotherapy, stem cells were returned via IV to reestablish bone marrow function.

Elements of the Hematopoietic System

• All the blood cells and their precursors
• The bone marrow, where blood cells originate
• The lymphoid tissues where some blood cells circulate, develop, and mature

Case Study Question 1

• What are the therapeutic advantages of an autologous stem cell transplant on Charlie’s bone marrow and immune system?

What is Blood?

• Specialized connective tissue
• Plasma suspends:
  • Red blood cells (erythrocytes)
  • White blood cells (leukocytes)
  • Platelets (thrombocytes)
• 7-8% of total body weight
• Adult blood volume: 5 – 6 liters
• Function of blood:
  • Carry gases and nutrients
  • Aid in body defenses
  • Prevent blood loss

Composition of Blood

• Fluid/dissolved components
  • Water
  • Proteins
  • Small molecular substances
• Cellular elements
  • Red blood cells
  • Thrombocytes or platelets
  • White blood cells
    • Lymphocytes
    • Leukocytes

Plasma Components

• Water: 90-91% of plasma volume
• Proteins: 6.5-8% of plasma volume
  • Albumin: 54% of plasma proteins
  • Globulins: 38% of plasma proteins
  • Fibrinogen: 7% of plasma proteins
• Other substances (1-2%):
  • Hormones, enzymes, carbohydrates, fats, amino acids, gases, electrolytes, excretory products

Plasma Proteins

• Albumin
  • Approximately 54% of plasma proteins
  • Contributes to plasma ONCOTIC pressure and maintenance of blood volume
  • Carrier for certain substances
• Globulins
  • Approximately 38% of plasma proteins
    • Alpha globulins: transport bilirubin and steroids
    • Beta globulins: transport iron and copper
    • Gamma globulins: antibodies of the immune system
• Fibrinogen
  • Approximately 7% of plasma proteins
  • Converted to fibrin in the clotting process
• SERUM: Plasma WITHOUT fibrinogen

Plasma vs Serum

• SERUM = PLASMA - FIBRINOGEN

Case Study Question 2

• Before harvesting stem cells, a cytokine growth factor is administered to the patient.
• What is the benefit of this procedure?

Blood Cells

• Erythrocytes—red blood cells (RBC’s)
  • Most numerous
  • LIFE SPAN ~120 days
  • Small, biconcave, contain no organelles
  • Easily deformed to move through small spaces
  • Carry oxygen on the hemoglobin molecule
  • Cellular fluid contains carbonic anhydrase to maintain acid-base balance

Granulocytes: Neutrophils

• Constitute 50% to 60% of white blood cells
• Primarily responsible for maintaining normal host defenses against invading substances
• First cells to arrive at the site of infection or injury
• Originate in the myeloblasts found in the bone marrow
• Move to the blood for 1-2 days after release from the marrow and then into the tissues for approximately 4-8 days
• Die in the tissue carrying out their phagocytic function or die of senescence

Granulocytes: Eosinophils

• 1% to 3% of the total number of white blood cells
• Increase in number during allergic reactions and parasitic infections
• Associated with allergic reactions
• In parasitic infections, eosinophils use surface markers to attach to the parasite and then release hydrolytic enzymes.

The Granulocytes: Basophils

• 0. 3% to 0.5% of the total leukocytes
• Consist of heparin (anticoagulant), histamine (vasodilator), and other mediators of inflammation
• Mast cells are derived from basophils
• Involved in allergic and hypersensitivity reactions

Not Granulocytes: Lymphocytes

• 20% to 30% of the total blood leukocytes
• Function in the lymph nodes or spleen to defend against microorganisms through the immune response
• Three types:
  • B-lymphocytes
  • T-lymphocytes
  • Natural killer cells

NOT GRANULOCYTES: Monocytes and Macrophages (M/M)

• Largest of the white blood cells
• In circulation for only 1-3 days
• 3% to 8% of the total leukocyte count
• Survive for months to years in the tissues
• Have different names when in the tissues
  • Kuppfer cells in the liver
  • Microglial cells in the brain
  • Histiocytes in the loose connective tissue
• Important role in chronic inflammation
• Involved in the immune response
  • M/Ms activate lymphocytes
  • M/Ms present antigens to T-cells

Thrombocytes, aka Platelets

• Circulating cell fragments of the large megakaryocytes
• Function to form the platelet plug to help control bleeding
• Platelet life: 7 to 10 days in circulation

Case Study Question 3

• Non-Hodgkin lymphoma is a disease involving B and T lymphocytes.
• What aspects of the immune response are these cells responsible for?

Question

• All of the following are cellular components of blood except which one?
  • A. Macrophages
  • B. Mast cells
  • C. Neutrophils
  • D. Eosinophils

Answer

• B. Mast cells
• Mast cells are not blood cells; they are found in connective tissue and initiate the inflammatory response. Mast cells are derived from the same hematopoietic stem cells as basophils but do not develop into mast cells until they leave the circulation and lodge in tissue sites.

Hematopoiesis

• Blood cells originate from pluripotent stem cells in the bone marrow.
• The proliferation, differentiation, and functional abilities of the various blood cells are controlled by cytokines.
• Cytokines are hormone-like growth factors

Major Maturation of Blood Cells

• Lymphocytes come from lymphoid stem cells.
• Everything else comes from myeloid stem cells.
• CFU-colony-forming unit; NK-natural killer cell

Hematopoietic Growth Factors

• Hematopoietic growth factors are used to:
  • Increase peripheral stem cells for transplantation
  • Accelerate cell proliferation after bone marrow engraftment

Useful Hematopoietic Growth Factors

• Colony Stimulating Factors (CSF’s)*
• EPO—erythropoietin
  • stimulates RBC production
• GM-CSF—granulocyte-monocyte colony-stimulating factor
  • stimulates granulocytes, monocytes, RBC’s, and megakaryocytes
• G-CSF—granulocyte colony-stimulating factor
  • stimulates neutrophils
• M-CSF—macrophage colony-stimulating factor
  • stimulates macrophages
• TPO—thrombopoietin
  • stimulates the differentiation of platelets

Conditions Responding to Use of Hematopoietic Growth Factors

• Bone marrow failure caused by chemotherapy or aplastic anemia
• Anemia of kidney failure
• Hematopoietic neoplasms
• Infectious diseases such as acquired immunodeficiency syndrome (AIDS)
• Congenital and myeloproliferative disorders
• Some solid tumors
  • HGF supports the bone marrow after significant chemotherapy used to treat solid tumors

Case Study Question 4

• When considering erythrocytes, how is the body able to meet hematopoietic demand in conditions such as hemolytic anemia or blood loss?

The Complete Blood Count

• A complete blood count provides information regarding the number of blood cells and their structural and functional characteristics.
• Hemoglobin
• Hematocrit
• Mean corpuscular volume (MCV)
• Mean corpuscular hemoglobin concentration (MCHC)
• Mean cell hemoglobin (MCH)
• The white cell differential count is the determination of the relative proportions (percentages) of individual white cell types.

Diagnostic Tests

• A complete blood count (CBC) is a commonly performed screening test that determines the number of red blood cells, white blood cells, and platelets per unit of blood.

Diagnostic Tests

• Blood count (CBC)
• Red cells and indices
• Erythrocyte sedimentation rate (ESR, sed rate)
  • non-specific screening test
  • used to follow chronic disease
• Bone marrow aspiration and biopsy
  • sternum and anterior iliac crest in children
  • posterior iliac crest in adults

Typical Complete Cell Count

• Red blood cell count
  • Male: 4.2-5.4 \times 10^6/\muL (4.2-5.4 \times 10^{12}/L)
  • Female: 3.6-5.0 \times 10^6/\muL (3.6-5.0 \times 10^{12}/L)
• White blood cell count:
  • 4.8-10.8 \times 10^3/\muL (4.8-10.8 \times 10^9/L)
• Differential count
  • Neutrophils: 50-73%
    • Segs
    • Bands: 0-4%
  • Eosinophils: 0-4%
  • Basophils: 0-2%
  • Lymphocytes: 20-44%
  • Monocytes: 3-8%
• Platelet count: 150-400 \times 10^3
• RBC indices
  • MCV (mean corpuscular volume): 80-100 fl.
  • MCH (mean cell hemoglobin): 27-34 pg/cell.
  • MCHC (mean corpuscular hemoglobin concentration): 31-35 g/dL.

Obtaining Blood Specimens

• Skin puncture (capillary blood)
• Venipuncture
• Arterial puncture
• Bone marrow aspiration

Case Study Answers

• What are the therapeutic advantages of an autologous stem cell transplant on Charlie’s bone marrow and immune system?
  • Stem cells are self-renewing and are able to continually proliferate. Removing these healthy cells before intensive chemotherapy or radiation therapy allows them to regenerate and repair damaged bone marrow once they are returned to the body. Using an autologous transplant maintains histocompatibility with the host.
• Before harvesting stem cells, a cytokine growth factor is administered to the patient. What is the benefit of this procedure?
  • The cytokine growth factor promotes the proliferation of stem cells and their migration from bone marrow. This provides more cells for rescue before the surgery and for later transplantation.
• Non-Hodgkin lymphoma is a disease involving B and T lymphocytes. What aspects of the immune response are these cells responsible for?
  • B lymphocytes are responsible for humoral-mediated immunity, and T lymphocytes are responsible for cell-mediated immunity.
• When considering erythrocytes, how is the body able to meet hematopoietic demand in conditions such as hemolytic anemia or blood loss?
  • Erythropoietin (EPO) is the cytokine responsible for triggering erythrocyte production. With persistent hemolysis or blood loss, there is resubstituting of red bone marrow for yellow. The spleen and liver can also participate in RBC production.