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

  1. Plasma (≈ $55\%$ of total volume)

  • >90\% water

  • Solutes: proteins, electrolytes, nutrients, gases, wastes

  • Similar to interstitial fluid due to capillary exchange of water/ions

  1. 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

1. 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

2. Eosinophils ($2!–!4\%$)

   • Attack multicellular parasites; phagocytose Ag-Ab complexes

   • Release NO & cytotoxic enzymes; modulate inflammation (counter mast cells)

   • Elevate in allergies & parasitic infections

3. Basophils (<$1\%$)

   • Migrate to injury; granules release histamine (vasodilator) & heparin (anticoagulant)

4. Monocytes ($2!–!8\%$)

   • Differentiate into macrophages after 24 h in blood

   • Large phagocytes; secrete chemotactic factors & fibroblast stimulants

5. 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.