A&PII
Chapter 18 – Blood (step-by-step, first-time learner style)
1. Big Picture: What Blood Does
Delivery System: Blood carries essential substances such as:
Oxygen (O₂)
Nutrients
Hormones
Pickup Service: Responsible for the removal of:
Carbon Dioxide (CO₂)
Wastes
Defense Force: Involves:
White Blood Cells (WBCs)
Antibodies
Clotting Factors
Regulator: Maintains homeostasis by regulating:
Temperature
pH Levels
Fluid Balance
2. Plasma vs Formed Elements
Plasma: The liquid component of blood.
Composed primarily of water
Contains proteins such as:
Albumin
Globulins
Fibrinogen
Formed Elements: The cellular components of blood which include:
Red Blood Cells (RBCs or Erythrocytes): Carry Oxygen
White Blood Cells (WBCs or Leukocytes): Provide defense
Platelets: Involved in clotting
3. Erythrocytes (RBCs) Structure & Function
Shape: Small, biconcave discs that provide:
Large Surface Area for optimal gas exchange
Cellular Composition:
No Nucleus and No Mitochondria: Adaptations for efficiency in O₂ transportation
Hemoglobin (Hb):
Packed within RBCs, responsible for binding to:
Oxygen (O₂)
Carbon Dioxide (CO₂)
4. Erythropoiesis – How RBCs Are Made
Figure 18.6 gives a visual representation of this process.
Goal: Produce adequate RBCs for sufficient O₂ delivery.
Location: Occurs in Red Bone Marrow.
Step-by-step Process:
Stem Cell (Hemopoietic Stem Cell):
Undifferentiated cell that can become any type of blood cell.
Erythrocyte CFU (Colony-Forming Unit):
Commits to becoming an RBC.
Erythropoietin (EPO) Stimulation:
Kidneys detect low O₂ levels (hypoxemia) and release EPO.
EPO signals bone marrow to increase RBC production.
Erythroblast:
Synthesizes hemoglobin.
The nucleus gradually shrinks and is eventually expelled.
Reticulocyte:
An immature RBC containing residual RNA.
Enters circulation; completes maturation within 1–2 days.
Mature Erythrocyte:
Fully matured RBC lacking a nucleus and organelles.
Typical lifespan of ~120 days.
Importance of Hypoxemia:
Conditions causing hypoxemia (such as blood loss, high altitude, or lung diseases) trigger kidney release of more EPO, leading to increased RBC production, thus normalizing oxygen levels.
5. Iron Metabolism
Refer to Figure 18.8 for details.
Importance of Iron: Essential for hemoglobin synthesis.
Step-by-step Process:
Dietary Iron:
Primarily exists as Fe³⁺ (ferric) and Fe²⁺ (ferrous) forms.
Stomach Acid converts Fe³⁺ to Fe²⁺ for absorption.
Gastroferritin:
A protein produced in the stomach that binds to Fe²⁺ to transport it to the small intestine.
Absorption & Transferrin:
Fe²⁺ is absorbed into the bloodstream.
Binds with Transferrin, a transport protein present in plasma.
Destination of Iron:
Bone Marrow: Used for hemoglobin synthesis in RBCs.
Muscle Tissue: For storage in Myoglobin.
Liver: Stores excess iron.
Storage in Liver:
Iron binds to Apoferritin to form Ferritin (the storage form of iron).
6. Erythrocyte Death & Disposal
Refer to Figure 18.9 for visualization.
Lifespan: RBCs live for about 120 days before becoming fragile.
Disposal Locations: Primarily the Spleen and Liver, where macrophages take action.
Step-by-step Breakdown Process:
Macrophage Breaks Down RBCs:
Hemoglobin is broken into its components - Globin and Heme.
Iron Handling:
Iron is extracted from heme for reuse or storage as ferritin.
Heme Conversion:
Transforming heme (lacking iron) into Biliverdin (green) which is further converted to Bilirubin (yellow).
Bilirubin Transport:
Bilirubin binds to Albumin in plasma for transport to the liver.
Excretion:
The liver secretes bilirubin into bile.
Bilirubin travels to the intestine and is excreted in feces (some bilirubin also exits via urine).
7. Erythrocyte Disorders
Polycythemia
Characterized by excessive RBC production resulting in abnormally thick blood.
Types:
Primary (Polycythemia Vera):
Occurs due to bone marrow cancer leading to uncontrolled RBC production.
Secondary:
Results from hypoxia (e.g., high altitude, smoking, or emphysema) or dehydration.
Dangers:
Increased viscosity can lead to:
Blood Clots
Stroke
Heart Strain
Anemia
Defined by insufficient RBCs or hemoglobin, leading to reduced oxygen-carrying capacity of blood.
Types:
Hemorrhagic Anemia: Following loss of blood.
Hemolytic Anemia: Caused by destruction of RBCs (e.g., due to sickle cell anemia or malaria).
Decreased Production:
Iron Deficiency
Pernicious Anemia (caused by vitamin B₁₂ deficiency)
Hypoplastic/Aplastic Anemia (failure of bone marrow)
Consequences of Anemia:
Hypoxia: Characterized by fatigue and shortness of breath (SOB).
Low Blood Osmolarity: Can lead to edema.
Low Blood Viscosity: Results in increased heart rate and lowered blood pressure (BP).
Sickle Cell Disease
Involves a mutation in the beta chain of hemoglobin resulting in HbS (sickled hemoglobin).
Under oxygen-deprived conditions, RBCs deform into a sickle shape causing:
Rigid, sticky characteristics leading to blockage of small blood vessels, causing pain and potential organ damage.
Hemolysis of sickled RBCs contributing to anemia.
Individuals with heterozygous genotype exhibit resistance to malaria.
8. Blood Types (ABO)
Key Definitions:
Antigen (Agglutinogen): Markers located on the RBC surface.
Antibody (Agglutinin): Proteins present in plasma, which bind to antigens.
Agglutination: The process wherein antibodies bind to RBC antigens causing clumping.
Blood Type Classifications:
Type A: Presence of antigen A on RBC with anti-B antibodies in plasma.
Type B: Contains antigen B with anti-A antibodies.
Type AB: Exhibits both A and B antigens; lacks anti-A or anti-B antibodies.
Type O: Absence of A/B antigens; possesses both anti-A and anti-B antibodies.
9. Rh Factor & Hemolytic Disease of the Newborn (HDN)
Rh+: Presence of D antigen.
Rh−: Absence of D antigen.
Problem Scenario:
If an Rh− mother carries an Rh+ baby, issues can arise if:
During delivery, fetal Rh+ blood enters the mother's bloodstream, prompting the mother to produce anti-D antibodies.
In a subsequent pregnancy with another Rh+ baby, the mother's anti-D antibodies may cross the placenta and attack the fetal RBCs, resulting in HDN (erythroblastosis fetalis).
Prevention:
Administration of RhoGAM (which are anti-D antibodies) to the Rh− mother to prevent her immune system from generating her own anti-D antibodies which could jeopardize future pregnancies.
10. Leukocytes (WBCs)
Leukocytes are essential for immune responses and are divided into:
Granulocytes:
Neutrophils:
Most abundant WBCs.
Act as first responders to bacterial infections.
Eosinophils:
Primarily target parasites and play a role in allergic reactions.
Basophils:
Release histamine (for vasodilation) and heparin (an anticoagulant).
Agranulocytes:
Lymphocytes:
Includes T cells, B cells, and natural killer (NK) cells, which are pivotal for adaptive immunity.
Monocytes:
Differentiate into macrophages in tissues where they perform phagocytosis.
11. Leukopoiesis
Refer to Figure 18.17 for visuals.
Process: Stem cells develop into different colony-forming units (CFUs) leading to the formation of specific types of WBCs.
Stimulated by: Colony-Stimulating Factors (CSFs).
Terms Related to WBCs:
Leukopenia: Low white blood cell count.
Leukocytosis: Elevated white blood cell count typically due to infection or allergy.
Complete Blood Count (CBC): A test that counts RBCs, WBCs, platelets, hemoglobin, etc.
12. Platelets & Hemostasis
Platelets:
Formed from megakaryocytes and are essential for blood clotting.
Normal Count: Ranges from 130,000–400,000/µL.
A low platelets count is referred to as Thrombocytopenia.
Thrombopoiesis
Process of platelet formation triggered by Thrombopoietin, which leads to:
Stem cells → Megakaryoblast → Megakaryocyte → Platelets.
13. Three Stages of Hemostasis
Vascular Spasm:
Immediate vasoconstriction at the site of injury to reduce blood loss.
Platelet Plug Formation:
Platelets adhere to exposed collagen at the injury site.
They degranulate to release serotonin, ADP, and thromboxane A₂, which recruit additional platelets to form a temporary plug.
Coagulation (Clotting):
Converts fibrinogen to fibrin, forming insoluble threads that stabilize the clot.
14. Clotting Pathways
Refer to Figure 18.21 for details.
Extrinsic Pathway:
Triggered by Tissue Factor (Factor III) released from damaged tissue.
Fast with fewer steps and involves Factors III, VII, leading to activation of Factor X.
Intrinsic Pathway:
Initiated by factors within the blood from platelet surfaces or damaged collagen.
Involves Factors XII, XI, IX, VIII, ultimately activating Factor X.
The Common Pathway involves:
Factor X → activates Prothrombin (II) → produces Thrombin → converts Fibrinogen (I) into Fibrin.
Note on Factors:
I = Fibrinogen
II = Prothrombin
III = Tissue Factor
Factor X: Common pathway
Factor VI is obsolete in clinical practice.
15. Clot Dissolution
Refer to Figure 18.23.
Plasmin: Enzyme responsible for dissolving fibrin.
Origination: Plasmin is derived from Plasminogen, activated by tissue plasminogen activator (tPA) and others.
16. Preventing Coagulation
Platelet Repulsion: Achieved by smooth endothelial cells of blood vessels.
Dilution: Normal blood flow aids in washing away clotting factors.
Anticoagulants: Substances like antithrombin and heparin act to prevent coagulation.
17. Clotting Disorders & Management
Hemophilia:
Involves a deficiency in clotting factors, leading to a failure of clot formation.
Thrombosis:
Abnormal clot formation in an unbroken vessel.
Management of Clots:
Prevention:
Use of Vitamin K antagonists (e.g., warfarin, coumarin) to decrease synthesis of clotting factors II, VII, IX, and X.
Dissolution:
Agents like Streptokinase, tPA, and hematin assist in breaking down clots.
Chapter 21 – Lymphoid & Immune Systems (first-time learner style)
1. Functions of the Lymphatic System
Think of the lymphatic system as:
Drainage System: Returns excess fluid back to the bloodstream.
Filter Network: Lymph nodes filter lymph for pathogens.
Fat Absorption: Lacteals in the small intestine absorb dietary lipids.
2. Components of the Lymphatic System
Lymph: The fluid recovered by lymphatic vessels.
Lymphatic Vessels: Structures that carry lymph throughout the body.
Lymphoid Tissue: Clusters of lymphocytes, such as MALT (mucosa-associated lymphoid tissue).
Lymphoid Organs: Includes nodes, tonsils, spleen, thymus, and bone marrow.
3. Lymphatic Capillaries
Structure: Closed at one end with overlapping endothelial cells forming valve-like flaps.
Functionality: Flaps are opened by high interstitial pressure, allowing fluid to enter.
Note: Absent from some tissues including the cornea, cartilage, bone, and bone marrow.
4. Lymphoid Tissues
Diffuse Lymphoid Tissue: Scattered lymphocytes found especially in mucosal tissues (MALT).
MALT: Mucosa-associated lymphoid tissue involved in gut immune response (e.g., Peyer's patches in the small intestine).
5. Lymphoid Organs
Primary Lymphoid Organs:
Red Bone Marrow: Site of B cell development.
Thymus: Site of T cell maturation.
Secondary Lymphoid Organs:
Lymph Nodes: Filter lymph and activate adaptive immune responses.
Tonsils: Guard pathways such as the pharynx for incoming pathogens.
Spleen: Filters blood, recycles RBCs, and carries out immune surveillance.
6. Innate vs. Adaptive Immunity
Innate Immunity:
Present from birth, not specific to pathogens, and lacks memory.
Localized response, except for systemic responses like fever.
Adaptive Immunity:
Specific immunity targeting particular antigens, characterized by memory, and systemic action.
7. Lines of Defense in Immunity
First Line: Skin and mucous membranes serve as barriers.
Second Line: Involves WBCs, natural killer cells, complement system, interferons, fever response, and inflammation.
Third Line: Adaptive immunity mediated by T cells, B cells, and antibodies.
8. External Barriers
Skin: Constitutes a physical barrier bolstered by keratin, acid mantle, and antimicrobial peptides.
Mucous Membranes: Produce mucus that traps microbes; secretion of lysozymes breaks down bacterial walls.
Hyaluronic Acid: Present in connective tissues helping to slow the dispersion of pathogens.
9. Leukocytes & Their Roles (Innate Side)
Neutrophils: Cells that target and kill bacteria.
Eosinophils: Primarily involved in combating parasites and mediating allergic responses.
Basophils: Release histamine and heparin to facilitate inflammatory responses.
Monocytes: Convert to macrophages for enhanced phagocytic activity.
Lymphocytes: Comprise innate and adaptive immune responses (NK cells, T cells, and B cells).
10. Antimicrobial Proteins
Interferons:
Released by virus-infected cells, acting to signal neighboring cells and activating NK cells and macrophages.
Complement System:
Comprises over 30 proteins; can be activated via:
Classical Pathway: Antibody-dependent activation.
Alternative & Lectin Pathways: Antibody-independent activation.
Outcomes of Activation:
Inflammation
Immune clearance
Opsonization (C3b): Enhancing phagocytosis.
Cytolysis (MAC): Forming a membrane attack complex that destroys pathogens.
11. Natural Killer (NK) Cells
Function to patrol and identify infected or cancerous cells.
Release perforins that create pores and granzymes to induce apoptosis in target cells.
12. Fever (Pyrexia)
A normal response to infection initiated by:
Exogenous Pyrogens: From microbial sources.
Endogenous Pyrogens: Produced by WBCs.
Raises the hypothalamic set point, benefiting the body in:
Increasing interferon production
Enhancing metabolism
Reducing microbial replication.
Phases of Fever:
Onset → Stadium → Defervescence.
Reye Syndrome: A serious complication that may occur when children are given aspirin during viral infections.
13. Inflammation
Purpose:
Limit the spread of pathogens.
Destroy pathogens or damaged tissue.
Remove debris.
Initiate repair processes.
Four Signs: Redness, heat, swelling, and pain are key indicators.
Steps of the Inflammatory Response:
Mobilization of Defenses:
Vasodilation (due to histamines and leukotrienes) increases blood flow → leads to redness and heat.
Increased vascular permeability permits plasma proteins and WBCs to leave bloodstreams → causing swelling (edema).
Margination: The process where WBCs adhere to vessel walls.
Diapedesis: Allowing WBCs to squeeze out of the capillaries into tissues.
Extravasation: Movement of WBCs into the tissue spaces.
Containment & Destruction:
Fibrinogen forms a wall around the affected area to contain pathogens.
Neutrophils arrive first to carry out phagocytosis and respiratory bursts.
Cytokines recruit additional immune cells.
Cleanup & Repair:
Macrophages dominate the cleanup phase; recycling dead cells and debris.
Edema aids in lymphatic drainage.
Pus is made up of dead neutrophils, bacteria, and debris, while an Abscess is a collection of trapped pus.
14. Adaptive Immunity Basics
Key Features:
Specificity: Ability to target specific pathogens.
Memory: Retains information for faster responses upon re-exposure.
Systemic: Involves the whole body.
Two Arms of Adaptive Immunity:
Cellular Immunity: T cells that directly attack infected cells.
Humoral Immunity: B cells that produce antibodies to tag pathogens for destruction.
15. Antigens, Epitopes, and Haptens
Antigen: Any substance that can bind to an antibody; delineates self from non-self.
Epitope: Specific site on an antigen recognized by the immune system.
Hapten: Small molecules that become antigenic only upon binding to a larger host protein (e.g., penicillin, poison ivy).
16. Antibody Structure & Classes
Antibody Monomer: Consists of 2 heavy and 2 light chains.
Variable Region: Contains the antigen-binding site.
Constant Region: Determines the antibody's class.
Antibody Classes:
IgA: Protects mucosal surfaces and provides passive immunity to newborns.
IgD: Serves as a B cell receptor and is involved in B cell activation.
IgE: Mediates allergies and responses to parasitic infections; stimulates eosinophils.
IgG: Most abundant antibody; involved in secondary responses and able to cross the placenta.
IgM: First antibody produced during the primary immune response; known for strong agglutination properties.
Key Questions Related to Antibody Classes:
Which is produced first? → IgM
Which is most abundant? → IgG
Which crosses the placenta? → IgG
17. Lymphocytes
NK Cells: Associated with the innate immune response.
T Cells: Part of adaptive immunity, maturing in the thymus.
B Cells: Part of adaptive immunity, maturing in the bone marrow.
18. Antigen-Presenting Cells (APCs) & MHC Proteins
APCs: Include dendritic cells, macrophages, and B cells that present antigens.
Major Histocompatibility Complex (MHC):
MHC I: Found on all nucleated cells, presenting antigens to CD8 (cytotoxic T cells).
MHC II: Found only on APCs, presenting to CD4 (helper T cells).
19. Cellular Immunity (T Cells)
Four Types of T Cells:
Cytotoxic T Cells (CD8): Attack and kill infected cells by binding to MHC I.
Helper T Cells (CD4): Coordinate the immune response by binding to MHC II.
Regulatory T Cells: Limit the immune system response to maintain homeostasis.
Memory T Cells: Provide long-term immunity against previously encountered pathogens.
NK vs. Tc Cells:
Natural Killer (NK) Cells: Part of the innate immune system and operate without needing MHC.
Cytotoxic T Cells (Tc): Part of the adaptive immune system and require antigen presentation on MHC I.
20. Humoral Immunity (B Cells)
Steps in B Cell Recognition:
Antigen binds to the B cell receptor.
B cell internalizes the antigen and presents it on MHC II.
A helper T cell binds and activates the B cell.
B cell undergoes clonal selection leading to the formation of Plasma Cells and Memory B Cells.
Effects of Antibodies:
Neutralization: Blocking active sites on toxins or viruses.
Complement Fixation: Activating the complement system.
Agglutination: Clumping of cells or pathogens.
Precipitation: Clumping of small antigens.
Role of Antibodies: Do not directly kill pathogens; instead, they tag them for destruction by other immune cells.
21. Memory: Primary vs. Secondary Response
Primary Response:
First exposure to an antigen; slower response; typically involves IgM first and then IgG.
Secondary Response:
Subsequent exposures; faster and more potent response; primarily involves IgG; often without causing illness.
Differences in Immunity Types:
Cellular Immunity: Involves T cells that directly attack infected cells.
Humoral Immunity: Involves B cells that produce antibodies found in bodily fluids.