Hormone released in response to low tissue oxygen levels (hypoxia): Stimulates stem cells and developing RBCs in red bone marrow.
Stimuli for EPO release include:
Anemia.
Reduced blood flow to kidneys.
Decreased O₂ content in lungs (due to disease or high altitude).
Lung damage.
Summary of Origins and Differentiation of Formed Elements
Lymphoid and myeloid stem cells give rise to different blood cell types.
EPO regulates RBC production and plays a key role during hypoxic states.
Section 2: Structure and Function of Formed Elements
Learning Outcomes
Define hematology and describe the elements of a complete blood count (CBC).
List characteristics and functions of RBCs; describe hemoglobin structure and functions.
Describe recycling of components from aged or damaged RBCs.
Module 4: Hematology
Definition and Importance
Hematology: The study of blood and blood-forming tissues; provides important information about a person’s health, detecting disorders (e.g., anemia, infection, clotting disorders).
Dyscrasias: Blood disorders that can have systemic effects.
Importance of Blood Tests
Reasons for performing blood tests:
Determine blood type.
Evaluate types and numbers of RBCs, WBCs, and platelets.
Assess abnormal values indicating underlying medical conditions.
Complete Blood Count (CBC)
Parameters assessed in 1 cubic millimeter (μL) of blood include:
RBC count.
WBC count.
Erythrocyte indices (hemoglobin levels).
Hematocrit.
Differential count; identifies numbers of each type of white blood cell.
Red Blood Cell Tests
Key Functions
Assess factors such as the number, size, shape, and maturity of circulating RBCs.
Can detect underlying issues such as internal bleeding that may not present with obvious signs.
Module 5: Red Blood Cells – Overview
Characteristics of Red Blood Cells (RBCs)
RBCs are the most common formed elements:
Approximately one-third of all cells in the body.
A single drop of blood contains ~260 million RBCs; average adult has ~25 trillion RBCs.
RBC Count Standard Test
Normal ranges:
Adult males: 4.5–6.3 million RBCs/μL.
Adult females: 4.2–5.5 million RBCs/μL.
Structure and Function
Physical Characteristics
Shape: Biconcave discs with thinner centers and thicker edges (7.2–8.4 μm).
Surface area-to-volume ratio: Increases efficiency for oxygen exchange.
Can form stacks (rouleaux) to facilitate transport through small vessels.
Flexibility: RBCs can maneuver through narrow capillaries.
Functional Aspects of RBCs
Losing organelles during development: Mature RBCs lack nuclei and ribosomes; this means they cannot divide or repair themselves.
Life span: Approximately 120 days.
Primary function: Transport respiratory gases, mainly oxygen.
Hemoglobin (Hb) content:
Males: 14–18 g/dL.
Females: 12–16 g/dL.
Hemoglobin Structure
Composition
Complex quaternary structure: Each hemoglobin molecule consists of:
Two alpha (α) chains.
Two beta (β) chains.
Similar to myoglobin in muscle cells, each chain contains a heme molecule.
O2 Binding Dynamics
Heme containing an iron ion: This interacts with an oxygen molecule to form oxyhemoglobin (HbO₂), imparting a bright red color to oxygenated blood.
The binding of oxygen is reversible:
Deoxyhemoglobin: Hemoglobin that is not bound to oxygen appears dark red.
Oxygen Transport Capacity
RBCs can carry over 1 billion oxygen molecules: Each RBC has ~280 million hemoglobin molecules, and each hemoglobin has four heme units.
Percentage of oxygen transported: Approximately 98.5% of oxygen is bound to hemoglobin; the rest is dissolved in plasma.
Module 6: Red Blood Cell Production and Breakdown
RBC Production – Erythropoiesis
Process of RBC renewal occurs continuously: About 1% of circulating RBCs are replaced daily (approximately 3 million new RBCs enter circulation every second).
Bone Marrow Role: Production occurs only in red bone marrow and can switch yellow marrow to red in response to severe blood loss.
Stages of development:
Erythroblasts begin producing hemoglobin.
Normoblasts lose their nuclei to become reticulocytes, which contain ~80% of the Hb of mature RBCs and enter the bloodstream.
Events in Macrophage Recycling
End of RBC life: Upon reaching the end of their lifecycle:
RBCs either rupture (hemolysis) or are engulfed by macrophages in the spleen, liver, or bone marrow.
Iron transport and recycling: Iron is transported in the bloodstream by transferrin after being stripped from hemoglobin.
Heme degradation: Heme is transformed from biliverdin to bilirubin and then transported to the liver.
Globin and Amino Acid Recycling: Globular proteins are disassembled, and amino acids are recycled for new protein synthesis.
Bilirubin Processing
Excretion and Recycling:
Bilirubin: Processed in the liver, excreted in bile. If bile system is obstructed, insufficient processing leads to elevated bilirubin, causing jaundice (yellow skin and eyes).
Kidneys: Excrete hemoglobin and urobilins, giving urine its yellow color; hematuria indicates intact RBCs in urine due to urinary tract damage.
Summary of RBC Production and Recycling
RBCs renew continually via erythropoiesis, with recycling managed through macrophages and complex biochemical pathways.
Module 7: Blood Typing and Immune Response
Blood Types Overview
Antigens: Substances that can stimulate an immune response; blood types are determined by surface antigens present on RBCs.
Surface antigens: >50 known blood cell surface antigens.
Key types: A, B, Rh (or D).
ABO Blood Group System
Classification based on presence/absence of A and B surface antigens:
Plasma contains antibodies that attack foreign antigens.
Four ABO blood types exist:
A, B, AB, and O.
Agglutination Process
Clumping of RBCs: Occurs when antigens are mixed with their corresponding antibodies, potentially leading to harmful blockages.
Rh Factor and Its Implications
Rh blood group classification: Based on the presence or absence of Rh surface antigens:
Rh+: Has the antigen.
Rh-: Lacks the antigen.
Included in blood type (e.g., O-, AB+).
Blood Type Distribution by Population
Percentages by Population
**United States Blood Type Distribution: **
O: ~< 49% to ~79% across different populations.
A: 27% to 40%.
B: 4% to 30%.
AB: <1% to 10%.
Blood Typing Tests and Procedures
Method: Mix blood drops with solutions containing antibodies against A, B, and Rh antigens; agglutination indicates the presence of specific antigens, assessing compatibility for transfusions.
Genetics of Blood Types
Genetic determination: Presence of anti-A and/or anti-B antibodies is genetically determined without prior exposure. Rh-negative individuals do not have anti-Rh antibodies until sensitized.
Summary of Blood Types
Importance of matching blood types during transfusions due to immune reactions associated with mismatched antigens.
Module 8: Clinical Implications of Blood Types
Hemolytic Disease of the Newborn (HDN)
Background: Condition caused by the interaction between maternal and fetal blood types, which can lead to serious health implications for newborns due to maternal antibodies crossing the placenta.
Most common scenario: Rh-negative mother with Rh-positive fetus; first pregnancy generally remains safe due to limited exposure of maternal blood to fetal cells.
Consequences of Blood Mixing
After delivery: Exposure to fetal Rh antigens during placental bleeding results in maternal sensitization to Rh antigens, leading to possible complications in subsequent pregnancies.
Maternal anti-Rh antibodies cross the placenta leading to hemolysis of fetal RBCs, known as erythroblastosis fetalis, which can be fatal without treatment.
Preventive Measures
Use of RhoGAM: Administered to Rh-negative mothers around weeks 26-28 of pregnancy to prevent sensitization by destroying fetal RBCs before maternal antibodies can be formed.
Summary of Hemolytic Disease
Understanding of potential complications and preventive treatments available to manage risks associated with maternal-fetal blood type incompatibilities.
Module 9: White Blood Cells (WBCs) and Immune Defenses
Overview of White Blood Cells
Characteristics of WBCs: Have nuclei and organelles, unlike RBCs, and play crucial roles in immune response.
Types of WBCs:
Neutrophils.
Lymphocytes.
Monocytes.
Eosinophils.
Basophils.
Shared Characteristics
Circulation duration: WBCs circulate for a brief period; most reside in tissues where infections occur.
Migration capability: WBCs can migrate out of circulation into tissues using diapedesis (emigration), responding to chemical stimuli via positive chemotaxis.
Phagocytosis: Neutrophils, eosinophils, and monocytes can engulf pathogens and debris; monocytes become macrophages upon entering tissues.
White Blood Cells Counts
Typical concentration: Approximately 7,000 WBCs per μL in blood; levels can increase during infection or inflammation.
Differential count: Indicates the proportion of each WBC type, important for diagnosing conditions.
Neutrophils: Main phagocytes during acute infections.
Eosinophils: Combat parasites and contribute to allergic reactions.
Basophils: Release histamine and promote inflammation.
Monocytes: Differentiate into macrophages in tissues.
Lymphocytes: Central role in adaptive immunity, including T and B cells.
Summary of White Blood Cells
Overview of types of WBCs and their functions in the immune response, essential for health and disease management.
Module 11: Blood Disorders
Identification and Diagnosis of Blood Disorders
Blood Sample Procurement
Venipuncture: Common procedure for obtaining blood samples from superficial veins, such as median cubital vein, due to ease and rapid sealing of veins.
Nutritional Blood Disorders
Iron deficiency anemia: Resulting from insufficient iron to form hemoglobin, leads to microcytic (small) RBCs. More common in women.
Pernicious anemia: Vitamin B12 deficiency, leading to macrocytic (large) RBCs. Caused by lack of intrinsic factor necessary for B12 absorption.
Calcium and vitamin K deficiencies: Affect clotting mechanisms; vitamin K is synthesized in the liver to make clotting factors.
Congenital Blood Disorders
Sickle Cell Disease: Genetic disorder where altered hemoglobin leads to sickle-shaped RBCs, causing fragility and blockage in vessels.
Hemophilia: Inherited bleeding disorder affecting primarily males; caused by lack of clotting factors, leading to severe bleeding.
Thalassemias: Disorders affecting the production of hemoglobin subunits, variability in severity.
Blood Infections
Bacteremia and viremia: Infections in blood without growth but detectable streams of pathogens.
Sepsis: Severe, widespread infection of body tissues; septicemia involves pathogens actively multiplying in blood, leading to life-threatening conditions.
Malaria: Transmitted by mosquitoes, characterized by cycles of fever due to infected erythrocyte ruptures.
Blood Cell Cancers
Leukemias: Cancers of blood-forming tissues characterized by overproduction of immature and abnormal WBCs.
Types: Myeloid leukemia and lymphoid leukemia.
Degenerative Blood Disorders
Disseminated intravascular coagulation (DIC): Dysfunctional coagulation leads to small clots blocking vessels and potentially uncontrolled bleeding due to fibrinogen depletion.
Summary of Blood Disorders
Comprehensive understanding of blood disorders including identification, causes, and implications for patient health across various conditions.