Composition and Function of Blood – Lecture Review
Composition of Whole Blood
Plasma: The liquid component that carries cells, nutrients, hormones, and waste products.
Red Blood Cells (Erythrocytes): Responsible for transporting oxygen from the lungs to the body and carbon dioxide from the body back to the lungs.
White Blood Cells (Leukocytes): Part of the immune system that helps fight infections and diseases.
Platelets (Thrombocytes): Essential for blood clotting and wound healing.
Whole blood: Composed of Plasma and Formed elements.
sample of blood: 55% plasma and 45% formed elements
Plasma: (46\text{--}63\%)
Water: (92\%) of plasma content.
Plasma proteins: (7\%) of plasma content.
Other solutes: (1\%) of plasma content.
Functions: Transports organic/inorganic molecules, formed elements, and heat; regulates osmotic pressure, clotting, and immunity (via antibodies).
Formed elements: (37\text{--}54\%)
Platelets: <0.1\%
White blood cells (WBCs): <0.1\%
Red blood cells (RBCs): 99.9\% of the formed-element fraction.
Plasma Details
Constitutes (55\%) of a standard blood sample.
Water (92\%\text{ of plasma}): Acts as a solvent and heat buffer.
Protein categories & roles (7\%\text{ of plasma}):
Albumins: Regulate osmotic pressure.
Fibrinogen: A clotting precursor that converts to fibrin.
Globulins/antibodies: Crucial for immune defense.
Red Blood Cells (Erythrocytes)
Description:
Most abundant blood cell type.
Lack a nucleus, providing more internal room for hemoglobin (Hb).
Biconcave disc shape: Increases surface-area/volume ratio, aiding gas diffusion.
Major Function: Transport gases (O$2$, CO$2$) via hemoglobin (Hb).
Hemoglobin (Hb)
Description:
Approximately 280\text{ million} Hb molecules per RBC.
Each Hb molecule consists of 2 (\alpha)-chains and 2 (\beta)-chains (globin proteins).
Each chain contains one heme group with a central Fe$^{2+}$ ion.
Function: Fe$^{2+}$ reversibly binds O$2$ and CO$2$.
Normal Concentration (Ranges):
Men: 14\text{--}18\,\text{g\,dL}^{-1}
Women: 12\text{--}16\,\text{g\,dL}^{-1}
White Blood Cells (Leukocytes)
Description:
Contain nuclei (often lobed).
Lack Hb, thus no gas transport function.
Diapedesis: Ability to pass between capillary endothelial cells to enter tissues.
Function: Most are phagocytic, engulfing and destroying pathogens or debris.
Two Classes:
1. Granular leukocytes (granulocytes):
Neutrophils (50\text{--}70\% of total WBCs):
Function: First responders at wounds; initiate infection control and phagocytize bacteria.
Eosinophils (2\text{--}4\% of total WBCs):
Function: Attack antibody-coated microbes/parasites; limit allergic responses.
Basophils (<1\% of total WBCs):
Function: Release histamine and other mediators at injury sites, leading to vasodilation and inflammation.
2. Agranular leukocytes:
Monocytes (2\text{--}8\% of total WBCs):
Function: Arrive second at a wound after neutrophils; phagocytize dead neutrophils and pathogens, then become macrophages in tissues.
Lymphocytes (20\text{--}30\% of total WBCs) (smallest WBC):
Function: Provide specific (adaptive) immunity.
T-cells: Directly attack and destroy foreign/virus-infected cells.
B-cells: Become plasma cells that secrete antibodies targeting specific antigens.
Platelets (Thrombocytes)
Definition: Cell fragments derived from megakaryocytes.
Function: Essential for hemostasis (stopping bleeding) and clot formation.
Hematocrit (Packed Red Cell Volume)
Definition: Measures the volume percentage of formed elements in whole blood.
Indicator: Reflects O$_2$-carrying capacity.
Low value: Indicates anemia or reduced oxygen transport capacity.
Average Ranges:
Males: 40\text{--}54\%
Females: 37\text{--}47\%
Blood Coagulation
Process: Blood outside the body gels within 3\text{--}4 minutes.
Mechanism: A cascade of enzymes converts fibrinogen into insoluble fibrin.
Fibrin threads: Form a mesh that traps platelets and RBCs, sealing the wound with a clot.
Clinical Relevance: Deficiencies (e.g., hemophilia) or hyper-coagulation (thrombosis) are significant clinical issues.
ABO Blood Group System
Phenotypes: Four main types: A, B, AB, O.
Determination: Based on the presence of surface antigens (agglutinogens) on RBC membranes.
Antigen A, Antigen B: Can appear singly, together, or be absent.
Plasma Content: Plasma contains antibodies (agglutinins) against antigens missing from the individual's own RBCs.
Type A: Has Antigen A on RBCs; Anti-B antibodies in plasma.
Type B: Has Antigen B on RBCs; Anti-A antibodies in plasma.
Type AB: Has Antigens A & B on RBCs; No Anti-A/Anti-B antibodies in plasma (universal recipient).
Type O: Has No A/B antigens on RBCs; Both Anti-A & Anti-B antibodies in plasma (universal donor).
Blood Typing Test: Involves mixing an RBC sample with anti-A & anti-B sera to observe agglutination (clumping).
Rh (D) Blood Group
Categories: Rh + and Rh - (negative).
Determination: Based on the presence of the D (Rh) antigen on RBCs.
Rh +: D antigen is present; No anti-D antibodies are present initially.
Rh -: D antigen is absent; initial lack of anti-D antibodies.
Antibody Production: Exposure to Rh+ blood (e.g., via transfusion or pregnancy) sensitizes the immune system, leading to anti-D antibody production in Rh- individuals.
Usage: Used in conjunction with ABO to specify full blood type (e.g., A+, O-).
Clinical Note: Erythroblastosis fetalis (hemolytic disease of the newborn) can be prevented by administering anti-D immunoglobulin (RhoGAM) to Rh- mothers.
Practical & Clinical Connections
Transfusion Safety: Matching donor/recipient blood types (ABO & Rh) is crucial to prevent adverse transfusion reactions (agglutination, hemolysis).
Diagnostic Indicators:
Hematocrit & Hb measurements: Inform about conditions like anemia, polycythemia, and oxygen-delivery issues.
WBC differentials: Aid in diagnosing infections, allergies, and leukemia.
Coagulation studies: Guide anticoagulant therapy and evaluate bleeding disorders.
Cardiovascular System: Macro-Overview
Consists of three integrated components:
Pump: The heart (generates pressure to move blood)
Conducting hoses: Hierarchical network of blood vessels
Fluid connective tissue: Blood (focus of this lecture)
Blood – Definition, Functions & General Properties
Specialized connective tissue with cells suspended in a fluid matrix
Five cardinal functions:
Transport: dissolved gases, nutrients, hormones, metabolic wastes
Regulation: pH & ionic composition of interstitial fluid
Restriction: clot formation limits fluid loss at injury sites
Defense: WBCs & antibodies neutralize toxins/pathogens
Stabilization of body temperature (heat distribution & dissipation)
Key physical characteristics:
Temperature ≈ (38^\circ \text{C} = 100.4^\circ \text{F})
High viscosity (≈ 5× water)
Slightly alkaline: \text{pH } 7.35!\text{–}!7.45
Total volume: \text{Blood (L)} \approx 0.07 \times \text{body mass (kg)}
Example: 75\,\text{kg} \Rightarrow 5.25\,\text{L} (≈ 5.4\,\text{qt})
Fractionation of Whole Blood
Yields two major fractions
Plasma (≈ 55\% of total volume)
>90\% water
Solutes: proteins, electrolytes, nutrients, gases, wastes
Similar to interstitial fluid due to capillary exchange of water/ions
Formed Elements
Red blood cells (RBCs/erythrocytes)
White blood cells (WBCs/leukocytes)
Platelets (cell fragments)
Plasma Proteins (≈ 7\% of plasma by mass)
Synthesized >90 % in the liver (exception: antibodies by plasma cells, peptide hormones by endocrine glands)
Albumins (≈ 60\%)
Major contributors to plasma osmotic pressure
Transport lipids: fatty acids, thyroid hormones, steroid hormones
Globulins (≈ 35\%)
Immunoglobulins (antibodies)
Transport globulins: hormone-binding proteins, metalloproteins, apolipoproteins, steroid-binding proteins
Fibrinogen (≈ 4\%)
Soluble precursor → fibrin (insoluble) during coagulation; removal leaves serum
Other proteins (≈ 1\%): enzymes, proenzymes, hormones
Formed Elements & Hemopoiesis
Hemopoiesis: continuous production in red bone marrow (myeloid tissue)
Stem cell base: Hemocytoblasts / Hematopoietic Stem Cells (HSCs)
Myeloid stem cells → RBCs, platelets, all WBCs except lymphocytes
Lymphoid stem cells → lymphocytes
Rough relative abundance:
RBCs: \approx 99.9\% of formed elements
WBCs: <0.1\% (5 major classes)
Platelets: cell fragments involved in clotting
Platelets (Thrombocytes)
Small, membrane-bound cytoplasmic packets shed by megakaryocytes
Count: 150{,}000!–!500{,}000\,\text{(\mu L^{-1})}; ≈ 1/3 stored in spleen & other vascular organs
Lifespan: 9!–!12 days; cleared by splenic phagocytes
Functions:
Release clotting chemicals (e.g.ADP, thromboxane A2)
Form temporary platelet plug
Actin–myosin contraction reduces break size (clot retraction)
Hormonal regulation: Thrombopoietin (TPO), IL-6, Multi-CSF
Production process (thrombocytopoiesis): megakaryocyte cytoplasm continually sheds platelets
Red Blood Cells (Erythrocytes)
Numbers & Indices
RBC count per \mu\text{L} whole blood:
Adult male: (4.5!–!6.3) \times 10^6
Adult female: (4.2!–!5.5) \times 10^6
Hematocrit (PCV) – percent formed elements
Male: 46\% (±5)
Female: 42\% (±5)
Hemoglobin concentration
Male: 14!–!18\,\text{g dL}^{-1}
Female: 12!–!16\,\text{g dL}^{-1}
Structural Specializations
Biconcave disc: thin center, thicker rim →
High surface-area/volume ratio ⇒ rapid gas diffusion
Formation of rouleaux stacks ⇒ smooth flow in narrow vessels
Flexibility: 7.8\,\mu\text{m} diameter RBC can traverse 4\,\mu\text{m} capillary
Anucleate; lack mitochondria & ribosomes → anaerobic metabolism, fixed lifespan (≈ 120 days)
Hemoglobin Architecture & Function
Quaternary protein: 4 globin chains (2 α, 2 β) each bound to a heme with central \text{Fe}^{2+}
Reversible O$_2$ binding:
Oxyhemoglobin \text{HbO}_2 (bright red) ↔ Deoxyhemoglobin (dark red)
At systemic capillaries (low O$2$): releases O$2$, binds CO$_2$ → Carbaminohemoglobin
At lungs (high O2): releases CO2, loads O2
Payload: each RBC ≈ 2.8\times10^8 Hb molecules → > 10^9 O$_2$ molecules per cell
Fetal Hb has higher O$_2$ affinity → facilitates placental uptake
Erythropoiesis & Regulation
Sites: embryo → liver/spleen/thymus; adult → red bone marrow (myeloid tissue)
Stages: Myeloid stem cell → Proerythroblast → (various) Erythroblast stages → Reticulocyte (ejects nucleus; enters circulation) → Mature RBC
Erythropoietin (EPO): glycoprotein hormone from kidneys (+ liver) in response to hypoxia; accelerates cell division & Hb synthesis, speeds reticulocyte maturation
Nutritional requirements: amino acids, Fe, folic acid, vitamins B${12}$ & B$6$ (B$_{12}$ deficiency → pernicious anemia)
Performance manipulation: Blood doping (autologous RBC reinfusion or exogenous EPO) elevates hematocrit but risks viscosity-induced cardiac events
RBC Turnover & Hemoglobin Recycling
~1\% of RBCs destroyed & replaced daily (≈ 3\times10^6\,\text{s}^{-1})
Aged RBCs phagocytosed by macrophages in spleen, liver, red marrow
Hemoglobin catabolism:
Globin → amino acids (recycled)
Heme iron → stored/transferred via transferrin; excess stored as ferritin/hemosiderin
Porphyrin ring → biliverdin (green) → bilirubin (yellow-orange) → liver bile → gut → urobilins/stercobilins (color feces & urine)
Pathologies:
Hemoglobinuria: free Hb in urine (brown/red) from excess intravascular hemolysis
Hematuria: whole RBCs in urine (renal vessel damage)
Jaundice: bilirubin accumulation from hepatic or duct obstruction
Blood Types & Immunohematology
Surface Antigens & Genetics
Erythrocyte membrane glycoproteins/lipids act as agglutinogens; inherited (codominant alleles)
ABO system: presence/absence of A & B antigens ⇒ four phenotypes
Type A: A antigen, plasma anti-B agglutinins
Type B: B antigen, plasma anti-A agglutinins
Type AB: A + B antigens, no anti-A/anti-B (universal recipient for cells)
Type O: no antigens, both anti-A & anti-B agglutinins (universal donor for cells)
Rh (D) antigen:
Rh⁺: antigen present
Rh⁻: antigen absent; develops anti-D only after sensitization (e.g.erythroblastosis fetalis)
>48 additional minor antigens → necessitate cross-matching
Transfusion Reactions (Cross-Reactions)
Occur when donor RBC agglutinogens interact with recipient plasma agglutinins → agglutination ± hemolysis → blocked vessels, Hb-mediated renal failure
Type O⁻: traditional universal donor, but compatibility testing (ABO + Rh + antibody screen) still mandatory
White Blood Cells (Leukocytes)
General Characteristics
Have nucleus & organelles, lack Hb
Distribution: majority reside in connective tissues & lymphoid organs; blood count: 5!\times!10^3!–!10\times!10^3\,\mu\text{L}^{-1}
Functional traits:
Emigration (diapedesis)
Amoeboid motility
Positive chemotaxis toward inflammatory signals
Phagocytosis (subset)
Major Classes
Neutrophils (polymorphonuclear; 50!–!70\%)
Pale granules with lysosomal enzymes + bactericidal compounds
Rapid phagocytes; perform degranulation releasing defensins
Secrete prostaglandins & leukotrienes (inflammation control)
Short half-life (≈ 10 h); accumulation forms pus
Eosinophils (2!–!4\%)
Attack multicellular parasites; phagocytose Ag-Ab complexes
Release NO & cytotoxic enzymes; modulate inflammation (counter mast cells)
Elevate in allergies & parasitic infections
Basophils (<1\%)
Migrate to injury; granules release histamine (vasodilator) & heparin (anticoagulant)
Monocytes (2!–!8\%)
Differentiate into macrophages after 24 h in blood
Large phagocytes; secrete chemotactic factors & fibroblast stimulants
Lymphocytes (20!–!40\%)
Constant recirculation between blood & lymphatic tissues
Three functional sub-classes:
T cells: cell-mediated immunity; cytotoxic & regulatory types
B cells: humoral immunity; differentiate → plasma cells (antibody secretion)
NK cells: immune surveillance; destroy abnormal (virus-infected/cancer) cells
Quantitative Diagnostics
Differential count identifies shifts pointing to infection, allergies, leukemia, etc.
Disorders:
Leukopenia: low WBCs
Leukocytosis: high WBCs (normal mild infection response)
Leukemia: extreme leukocytosis; malignant clones
Leukopoiesis & Regulation
Hemocytoblast →
Myeloid stem cells → granulocytes & monocytes via progenitor cells
Lymphoid stem cells → lymphocytes (B, T, NK); T cell maturation in thymus
Colony-Stimulating Factors (CSFs) fine-tune populations:
Multi-CSF: broad (RBCs, platelets, granulocytes, monocytes)
GM-CSF, G-CSF, M-CSF act selectively
Hemostasis (Cessation of Bleeding)
1. Vascular Phase (Immediate – \le 30 min)
Vascular spasm: smooth-muscle contraction ↓ vessel diameter
Endothelial responses:
Expose basement membrane
Release ADP, tissue factor (Factor III), prostacyclin, endothelins (peptide vasoconstrictors)
Membranes become sticky → opposing surfaces seal micro-tears
2. Platelet Phase (Starts \approx 15 s)
Platelet adhesion to exposed collagen/basement membrane (via von Willebrand factor)
Platelet aggregation → platelet plug
Activated platelets secrete:
ADP (platelet activator)
Thromboxane A$_2$ & serotonin (vascular spasm enhancers)
Clotting factors, PDGF (promotes vessel repair), \text{Ca}^{2+}
Growth limiting mechanisms: prostacyclin, WBC-derived inhibitors, enzymatic ADP breakdown, negative feedback by serotonin, isolation by developing fibrin clot
3. Coagulation Phase (Starts \ge 30 s)
Cascade requiring 11 plasma proteins (proenzymes) + \text{Ca}^{2+} & vitamin K dependent synthesis
Extrinsic pathway: damaged tissue → Factor III + Ca^{2+} + Factor VII → activates Factor X
Intrinsic pathway: contact activation (collagen/PF-3) sequentially activates Factors XII → XI → IX → VIII → Factor X
Common pathway:
Factor X → prothrombin activator
Prothrombin → thrombin
Thrombin converts fibrinogen → fibrin strands (framework of clot)
Thrombin also positive-feedbacks extrinsic (↑ Factor III) & intrinsic (↑ PF-3) pathways ⇒ rapid amplification
Regulation / Limitation of Clot
Anticoagulants (endogenous):
Antithrombin III: inhibits thrombin & Factors IX, X
Heparin: from basophils/mast cells; accelerates antithrombin III
Thrombomodulin (endothelium) + thrombin → activates Protein C (inactivates Factors V & VIII, ↑ plasmin)
Prostacyclin: opposes platelet aggregation
Essential cofactors: \text{Ca}^{2+} (all pathways) & vitamin K (synthesis of Factors II, VII, IX, X)
Pathologies:
Thrombocytopenia (low platelets)
Hemophilia (Factor VIII/IX deficiency)
Thrombophilia (tendency to clot)
DVT (deep vein thrombosis)
Clot Retraction & Fibrinolysis
Retraction (mins–hrs): platelet actin–myosin pulls fibrin, draws wound edges together, ↓ residual bleeding
Fibrinolysis (clot removal): thrombin + t-PA activate plasminogen → plasmin; plasmin enzymatically digests fibrin network
Integration & Clinical Connections
Temperature homeostasis: blood rerouting to skin dissipates heat; shunting conserves heat
Anemia: ↓ O2 delivery triggers fatigue, pallor, tachycardia; etiologies include iron deficiency, pernicious, aplastic, hemolytic, hemorrhagic
Polycythemia/high hematocrit: ↑ viscosity → ↑ afterload & thrombosis risk
Leukemia treatments often exploit CSF manipulation & bone marrow transplantation
Anticoagulant therapy: heparin (acute), warfarin (vit K antagonist), direct Xa inhibitors; require monitoring of clotting times
Transfusion medicine: pre-transfusion type & screen, cross-match, Rh prophylaxis (RhoGAM) for Rh⁻ mothers
Here are quick bullet points on active, passive, and adaptive immunity:
Active Immunity:
Occurs when an individual's own immune system produces antibodies and memory cells in response to direct exposure to an antigen (e.g., natural infection or vaccination).
Provides long-lasting protection because the body remembers the pathogen.
Passive Immunity:
Occurs when an individual receives pre-formed antibodies from another source (e.g., mother to fetus via placenta, anti-venom).
Provides immediate but temporary protection because the body does not create its own memory cells or antibodies.
Adaptive (Specific) Immunity:
A highly specific type of immunity that develops throughout an individual's life in response to exposure to specific pathogens or antigens.
Involves specialized cells:
T-cells: Directly attack and destroy foreign or virus-infected cells.
B-cells: Become plasma cells that secrete antibodies targeting specific antigens.
Characterized by memory, allowing for a faster and stronger response upon subsequent exposure to the same pathogen.