Blood Chapter Notes (Functions, Composition, Plasma, Formed Elements, Clotting, Blood Grouping, Diagnostics)

Functions of Blood

• Blood is a fluid connective tissue composed of plasma (extracellular matrix) and formed elements (cells and cell fragments).

• Blood functions to maintain homeostasis through:

  • Transport of gases, nutrients, and wastes.
  • Transport of processed molecules and regulatory molecules (e.g., hormones).
  • Regulation of pH and osmosis; maintenance of osmotic balance and acid-base balance.
  • Temperature regulation via heat exchange as blood circulates.
  • Protection against foreign substances (immune components).
  • Clot formation to prevent excessive blood loss and aid tissue repair.

• Blood is pumped by the heart and flows through vessels to reach all body areas.

• Key pH range for blood: $7.35-7.45$.

• Diagnostic value: Blood composition provides insights into health and disease through laboratory tests.

Composition of Blood

• Blood is a type of connective tissue with a liquid matrix (plasma) and formed elements (cells and fragments).
• Volume composition:
  • Plasma accounts for roughly $55\%$ of blood volume.
  • Formed elements account for roughly $45\%$ of blood volume.
  • Total blood volume in adults: ≈ $4-5\,\text{L}$ (female) and ≈ $5-6\,\text{L}$ (male).
  • Blood makes up about $8\%$ of total body weight.
• Plasma and formed elements are separated by a buffy coat: plasma on top, buffy coat (white blood cells + platelets) in the middle, and red blood cells (RBCs) at the bottom.
• Plasma components and their functions (Table summary):
  • Water: about $91\%$ by volume; solvent and suspending medium.
  • Proteins: about $7\%$ by volume; includes albumin, globulins, fibrinogen; aid osmotic balance, transport, immunity, and clotting.
  • Ions, nutrients, gases, waste products, regulatory substances: about $2\%$ by volume; various roles in transport, buffering, metabolism.
• Major plasma proteins:
  • Albumin: $58\%$ of plasma proteins; contributes to osmotic pressure and water balance.
  • Globulins: $38\%$ of plasma proteins; include antibodies (immune defense), transport proteins, and some clotting factors.
  • Fibrinogen: $4\%$ of plasma proteins; essential for clot formation (fibrin formation from fibrinogen).
• Serum = plasma without clotting factors.
• Albumin and globulins also function in transport (binding and carrying hormones, lipids, etc.).
• Osmotic and acid-base context:
  • Osmotic pressure in part maintained by albumin; Na\, and Cl- contribute to osmotic balance and membrane potentials.
  • Plasma participates in acid-base balance via buffering.
• Regulatory substances in plasma (hormones, enzymes) coordinate systemic functions.

Plasma

• Plasma is a pale yellow fluid: $\text{Plasma} = \text{water} + \text{proteins} + \text{ions} + \text{nutrients} + \text{gases} + \text{waste} + \text{regulatory substances}$.
• Normal plasma composition:
  • Water ~ $91\%$.
  • Proteins ~ $7\%$ (albumin, globulins, fibrinogen).
  • Other components ~ $2\%$ (ions, nutrients, gases, wastes, regulatory substances).
• Blood plasma volume remains relatively constant due to intake/output balance.
• Gas transport:
  • Oxygen (O₂) enters via lungs; carbon dioxide (CO₂) exits via lungs.
  • CO₂ transport involves bicarbonate ions, Hb, and plasma.
  • Approximate CO₂ transport distribution: $\sim 70\%$ as $\text{HCO}_3^-$, $\sim 23\%$ bound to Hb or other proteins, $\sim 7\%$ dissolved in plasma.
• Carbonic anhydrase (CA) catalyzes: $\mathrm{CO<em>2 + H</em>2O \rightleftharpoons H^+ + HCO_3^-}$ (
  located mainly inside RBCs).
• Hemoglobin (Hb) and carbon monoxide (CO): CO binds Hb about $210\times$ more readily than O₂, reducing O₂ transport.

Formed Elements

• Formed elements constitute about $45\%$ of blood volume and include:
  • Red blood cells (RBCs, erythrocytes) ≈ $95\%$ of formed elements.
  • White blood cells (WBCs, leukocytes) ≈ $5\%$ of formed elements.
  • Platelets (thrombocytes) – cell fragments; very small but essential for clotting.
• Relative abundance:
  • RBCs are about 700 times more numerous than WBCs and about 17 times more numerous than platelets.
• Origin: All formed elements arise from hematopoietic stem cells (HSCs, hemocytoblasts).
• Hematopoiesis overview:
  • HSCs differentiate into two intermediate lineages: myeloid stem cells and lymphoid stem cells.
  • Most formed elements derive from myeloid stem cells; lymphoid stem cells give rise to lymphocytes.
  • Growth factors regulate each lineage and the total yield.

Red Blood Cells (RBCs)

• Structure and function:
  • Normal RBCs are disk-shaped with a biconcave shape, increasing surface area for gas exchange.
  • They lose nuclei and most organelles during maturation; lifespan ≈ $120\ \text{days (males)}$ and $110\ \text{days (females)}$.
  • Hemoglobin (Hb) ~ one-third of RBC volume; responsible for red color and O₂ transport.
• Hemoglobin structure:
  • Hb consists of four globin chains and four heme groups: $\text{Hb} = 4\ \text{globin} + 4\ \text{heme}$.
  • Each heme contains one iron (Fe) atom that reversibly binds O₂.
  • Hb quaternary structure includes two alpha ((\alpha)) and two beta ((\beta)) globin chains.
  • Each Hb molecule can bind up to four O₂ molecules (one per heme).
• O₂ transport specifics:
  • Hb bound to O₂ is bright red; Hb without O₂ is darker red.
  • Approximately $98.5\%$ of O₂ is transported bound to Hb; about $1.5\%$ is dissolved in plasma.
• CO₂ transport specifics:
  • CO₂ is produced by tissues and transported back to lungs by three pathways:
  • Carbonic acid/bicarbonate system inside RBCs: $\mathrm{CO<em>2 + H</em>2O \rightleftharpoons H^+ + HCO_3^-}$
  • Bound to Hb or other proteins (about $23\%$).
  • Dissolved in plasma (about $7\%$).
• Iron and copper in Hb:
  • Two-thirds of the body's iron is in Hb.
  • Iron in the diet replenishes losses; iron recycling is a major process.
  • Iron needs are higher in females due to menstruation.
• RBC production and regulation:
  • Erythropoiesis occurs in red bone marrow; stimulated by low blood O₂ levels via erythropoietin (EPO) from the kidneys.
  • Vitamins required: folate (B9) and B12 for DNA synthesis; iron for Hb formation.
  • Stages of erythroid development: myeloid stem cell → proerythroblast → early erythroblast → late erythroblast → reticulocyte → mature RBC.
  • Negative feedback: low O₂ → ↑EPO → ↑RBC production → ↑O₂ transport.
• Hemoglobin breakdown and iron recycling:
  • When RBCs are removed by macrophages (spleen, liver), Hb is broken down:
    1) Globin chains → amino acids reused.
    2) Heme → Fe recycled to marrow; iron transported in blood for reuse.
    3) Heme minus iron → bilirubin → liver excretion into bile; in urine if excreted directly.
  • Jaundice can occur if bilirubin builds up due to liver/d bile flow issues.

White Blood Cells (WBCs)

• General features:
  • WBCs are nucleated and lack Hb; they can migrate out of blood to tissues (ameboid movement).
  • Two main groups: granulocytes (neutrophils, basophils, eosinophils) and agranulocytes (lymphocytes, monocytes).
• Neutrophils (granulocytes):
  • Most common WBC type; multilobed nucleus; granular cytoplasm.
  • Life in blood is ~ $10-12\ \text{hours}$; migrate to tissues to phagocytize microorganisms.
  • Dead neutrophils and debris can form pus.
• Basophils (granulocytes):
  • Least common; large cytoplasmic granules stain blue/purple.
  • Release histamine (inflammation) and heparin (prevents clotting).
• Eosinophils (granulocytes):
  • Red/orange granules; two-lobed nucleus.
  • Involve in inflammatory response, allergies, asthma; combat certain worm parasites.
• Lymphocytes (agranulocytes):
  • Smallest WBCs; produce antibodies and other immune chemicals; various subtypes.
  • Involved in antibody production, graft rejection, tumor control, immune regulation (see Chapter 14).
• Monocytes (agranulocytes):
  • Largest WBCs; differentiate into macrophages in tissues; phagocytose bacteria, dead cells, debris.
  • Present processed antigens to lymphocytes to activate immune responses.
• Clinical notes:
  • Positive chemotaxis: WBCs move toward chemical signals to reach sites of infection/inflammation.
  • Differential WBC count helps diagnose infections and allergies (e.g., high neutrophils in bacterial infection; high eosinophils/basophils in allergic reactions).

Platelets

• Platelets are small cell fragments derived from megakaryocytes in red bone marrow.
• They form platelet plugs to seal small vessel breaks and release chemicals necessary for clotting.

Preventing Blood Loss (Hemostasis)

• Hemostasis involves three coordinated processes: vascular spasm, platelet plug formation, and blood coagulation (clotting).

Vascular Spasm

• Immediate, temporary constriction of damaged vessel due to smooth muscle contraction.
• Stimulated by chemicals released by damaged vessel walls and platelets (e.g., thromboxanes from platelets; endothelin from endothelial cells).

Platelet Plug Formation (Primary Hemostasis)

• Platelet plug seals small breaks; steps occur rapidly and in parallel:
  1) Platelet adhesion: Platelets bind exposed collagen via von Willebrand factor, linking platelets to damaged vessel wall.
  2) Platelet release reaction: Platelets release ADP and thromboxane, activating additional platelets (positive feedback).
  3) Platelet aggregation: Fibrinogen bridges connect activated platelets via fibrinogen receptors, forming a platelet plug.
• Clinical note: Inhibition of platelet activation (e.g., by aspirin) reduces plug formation and lowers clot risk but increases bleeding risk.

Blood Clotting (Coagulation)

• Clot formation is a secondary hemostatic process that forms a fibrin network trapping cells and platelets.

• Clotting factors are mostly plasma proteins synthesized in the liver; many require vitamin K and Ca²⁺.

• Three-stage overview (Figure 11.11):
  1) Prothrombinase production: Activation of clotting factors leads to formation of prothrombinase (the prothrombin activator).
  2) Thrombin production: Prothrombinase converts prothrombin to thrombin.
  3) Fibrin production: Thrombin converts fibrinogen to fibrin, forming the clot.

• Key regulatory/controlling elements:

  • Anticoagulants (e.g., antithrombin, heparin) inactivate thrombin and prevent excessive clotting.
  • Vitamin K-dependent clotting factors; calcium; platelet-derived chemicals influence the cascade.

• Thrombus vs embolus:

  • Thrombus: clot attached to vessel wall.
  • Embolus: detached clot circulating in the bloodstream.

• Fibrinolysis: Clot dissolution via plasmin, generated from plasminogen by thrombin, t-PA, or other activators (e.g., streptokinase).

• Clinical therapies: Plasmin activators (e.g., t-PA) dissolve clots during heart attack treatment; aspirin and anticoagulants prevent clot formation; warfarin inhibits vitamin K-dependent factor synthesis.

• Clot retraction and wound repair:

  • Platelets contract via actin-myosin, pulling fibrin threads together to tighten the clot and pull vessel edges inward.
  • Serum is squeezed from the clot; tissue repair proceeds with fibroblast and epithelial cell activity.

Blood Grouping and Transfusion

• Transfusion vs infusion:

  • Transfusion: transfer of blood/blood components between individuals.
  • Infusion: introduction of a fluid other than blood (e.g., saline).

• Historical transfusion reactions occur when antigens and antibodies interact (agglutination and hemolysis).

• Antigens and antibodies:

  • Red blood cell surface antigens elicit antibodies in plasma if foreign antigens are encountered.
  • Agglutination: clumping due to antigen–antibody bridges; hemolysis can occur from ruptured cells.
  • Normal antibody development against A/B antigens typically occurs after exposure; anti-A and anti-B antibodies are present in plasma for most adults but not in newborns.

• ABO blood group system:

  • Antigens present on RBC surfaces: A and B; possible combinations:
  • Type A: A antigen; anti-B antibodies in plasma.
  • Type B: B antigen; anti-A antibodies in plasma.
  • Type AB: both A and B antigens; no anti-A or anti-B antibodies in plasma.
  • Type O: neither A nor B antigens; both anti-A and anti-B antibodies in plasma.
  • Distribution (U.S. White population): $ext{O} = 47\%, \text{A} = 41\%, \text{B} = 9\%, \text{AB} = 3\%.$
  • Distribution (U.S. Black population): $\text{O} = 46\%, \text{A} = 27\%, \text{B} = 20\%, \text{AB} = 7\%.$

• Rh system:

  • Rh-positive means presence of Rh antigens on RBCs; Rh-negative means absence.
  • About $85\%$ of whites and $95\%$ of blacks are Rh-positive.
  • Rh antigens: antibodies against Rh do not normally exist; they develop only if an Rh-negative individual is exposed to Rh-positive RBCs (transfusion or placental transfer).
  • HDN (Hemolytic Disease of the Newborn) can occur when an Rh-negative mother carries an Rh-positive fetus and becomes sensitized; anti-Rh antibodies cross the placenta in subsequent pregnancies and destroy fetal RBCs.

• Rh incompatibility prevention: RhoGAM (Rho(D) immune globulin) injections during pregnancy and after delivery prevent sensitization by binding Rh antigens from fetal cells that may enter the maternal circulation.

• Diagnostic scenario (HDN): testing and possible interventions (e.g., exchange transfusion) to manage fetal anemia; monitoring of anti-Rh antibody levels in the mother.

• Type and Crossmatch:

  • Blood typing determines ABO and Rh groups by agglutination tests with known antisera.
  • Crossmatch tests donor cells against recipient serum and donor serum against recipient cells to ensure no agglutination; a safe match shows no agglutination in either direction.

• Blood typing visuals: agglutination patterns indicate antigen presence or absence (illustrative figures in the text).

• Universal donor/recipient caveats:

  • Type O cells lack A/B antigens and are commonly labeled universal donors, but other incompatibilities (e.g., Rh) and other antigen systems can still cause reactions. Type AB donors are often labeled universal recipients for plasma compatibility, but plasma antibodies complicate this simplification.

Diagnostic Blood Tests and Normal Values

• Complete Blood Count (CBC): provides a broad view of hematologic health and includes:
  • Red blood cell (RBC) count; hemoglobin (Hb) level; hematocrit (Hct); white blood cell (WBC) count; differential WBC counts; platelet count.
• RBC counts (normal values):
  • Male: $4.6-6.2 \times 10^6/\mu\text{L}$
  • Female: $4.2-5.4 \times 10^6/\mu\text{L}$
• Hemoglobin (Hb) normal values (grams per 100 mL):
  • Male: $14-18\ \text{g/dL}$
  • Female: $12-16\ \text{g/dL}$
• Hematocrit (Hct) normal values (percentage):
  • Male: $40-52\%$
  • Female: $38-48\%$
• WHITE BLOOD CELLS (WBC) and differential:
  • Normal total WBC: $5,000-9,000/\mu\text{L}$
  • Differential (percentages):
  • Neutrophils: $60-70\%$
  • Lymphocytes: $20-25\%$
  • Monocytes: $3-8\%$
  • Eosinophils: $2-4\%$
  • Basophils: $0.5-1\%$
• Platelets: normal count $250,000-400,000/\mu\text{L}$
• Anemia definitions and notes:
  • Anemia = deficiency of normal Hb or RBCs; Hb and/or RBC count are reduced.
  • Various causes covered in the chapter (nutritional, aplastic, hemorrhagic, hemolytic, thalassemia, sickle-cell, etc.).
• Blood chemistry indicators and tests:
  • Blood glucose, BUN (blood urea nitrogen), bilirubin, cholesterol, etc., provide clues to organ function and disease states.

Doping, Disorders, and Clinical Impacts

• Blood doping increases circulating RBCs to improve oxygen delivery; risks include erythrocytosis and vascular complications.
• Hemophilia and von Willebrand disease are clotting disorders that affect clot formation and platelet function.
• Disseminated intravascular coagulation (DIC) is a pathology involving widespread clotting followed by bleeding; caused by severe tissue damage or other triggers.
• Anticoagulant therapies (e.g., heparin, warfarin) manage clotting disorders; balance between preventing clots and causing bleeding is critical.

Summary Points (Key Takeaways)

• Blood has seven major functions: transport, protection, regulation, and clotting as part of tissue repair.
• Plasma (55% of blood) contains water, proteins (albumin, globulins, fibrinogen), ions, nutrients, gases, wastes, and regulatory substances; serum is plasma without clotting factors.
• Formed elements (45%): RBCs (most abundant), WBCs, and platelets; all originate from hematopoietic stem cells; RBCs have a 120-day lifespan in males and 110 days in females.
• RBCs transport O₂ via hemoglobin (Hb), which contains four globin chains and four heme groups each with Fe; CO binds Hb with high affinity; majority of CO₂ is transported as bicarbonate via carbonic anhydrase-catalyzed reaction inside RBCs.
• Platelets form plugs and participate in coagulation; the clotting cascade involves prothrombinase, thrombin, and fibrin formation, with Ca²⁺ and vitamin K dependencies; clots are dissolved by plasmin in fibrinolysis.
• Blood groups ABO and Rh are critical for transfusions; mismatches cause agglutination/hemolysis; compatibility is ensured via typing and crossmatching; HDN prevention uses RhoGAM in Rh-negative mothers.
• CBC and related tests (RBC count, Hb, Hct, WBC count, differential, platelet count, prothrombin time) provide diagnostic insight into anemia, infection, clotting disorders, and general health.
• Nutritional and pharmacological factors (iron, folate, B12, vitamin K, anticoagulants) have major impacts on blood cell production, clotting, and overall hematologic health.