Chapter 17: Blood – Structure, Function, and Disorders

Blood: Overview and Functions

General Functions of Blood

Blood is a vital connective tissue that serves as the transport medium of the cardiovascular system. It performs three primary functions:

• Transport: Delivers oxygen (O2) and nutrients to body cells, removes metabolic wastes (such as carbon dioxide and urea) to lungs and kidneys for elimination, and transports hormones from endocrine organs to target tissues.

• Regulation: Maintains body temperature by absorbing and distributing heat, regulates pH using buffers (notably the bicarbonate ion), and sustains adequate fluid volume in the circulatory system.

• Protection: Prevents blood loss via clot formation (plasma proteins and platelets) and defends against infection through immune cells and antibodies.

Blood Composition

Components of Blood

• Tissue Type: Blood is a specialized connective tissue.

• Matrix: The matrix is plasma, which makes up about 55% of blood volume.

• Formed Elements: These include erythrocytes (red blood cells, RBCs), leukocytes (white blood cells, WBCs), and platelets (cell fragments).

Blood color varies with oxygen content: high O2 levels yield scarlet red, low O2 levels yield dark red. The pH of blood is tightly regulated between 7.35 and 7.45.

Blood Plasma

• Physical Properties: Straw-colored, sticky fluid; about 90% water.

• Solutes: Contains over 100 dissolved solutes, including nutrients, gases, hormones, wastes, proteins, and inorganic ions.

• Plasma Proteins: Most abundant solutes, produced mainly by the liver. Albumin (60% of plasma proteins) acts as a carrier, blood buffer, and contributes to plasma osmotic pressure.

Erythrocytes (Red Blood Cells)

Structural Characteristics

• Small-diameter (7.5 μm), biconcave disc shape, anucleate, and lack organelles.

• Filled with hemoglobin (Hb) for gas transport.

• Flexible membrane due to spectrin and other proteins.

• Biconcave shape increases surface area for gas exchange.

• Hemoglobin constitutes 97% of cell volume; no mitochondria (energy from anaerobic glycolysis).

Hemoglobin Structure and Function

• Hemoglobin binds reversibly with oxygen.

• Composed of four polypeptide chains (2 alpha, 2 beta), each with a heme group.

• Each heme’s central iron atom binds one O2 molecule.

• Each Hb molecule can transport four O2 molecules.

• Each RBC contains about 250 million Hb molecules.

• Oxyhemoglobin: Hemoglobin bound to O2 (bright red).

• Deoxyhemoglobin: Hemoglobin after releasing O2 (dark red).

• About 20% of CO2 in blood binds to Hb, forming carbaminohemoglobin.

Hematopoiesis

Hematopoiesis is the formation of all blood cells, occurring in red bone marrow (axial skeleton, girdles, proximal epiphyses of humerus and femur in adults). Hematopoietic stem cells (hemocytoblasts) give rise to all formed elements. Hormones and growth factors direct cell differentiation; committed cells cannot change lineage.

Erythropoiesis: Formation of RBCs

• Takes about 15 days.

• Stages:

  1. Hematopoietic stem cell → myeloid stem cell (committed cell)

  2. Myeloid stem cell → proerythroblast

  3. Proerythroblast divides, forms basophilic erythroblasts (ribosome synthesis begins)

  4. Basophilic erythroblasts synthesize ribosomes (blue-staining)

  5. Polychromatic erythroblasts synthesize hemoglobin (pink and blue areas)

  6. Orthochromatic erythroblasts (mostly hemoglobin, pink; nucleus ejected, concave shape)

  7. Reticulocytes (still contain ribosomes; mature into erythrocytes in 2 days)

• Reticulocyte count indicates rate of RBC formation.

Regulation and Requirements

• Too few RBCs: tissue hypoxia.

• Too many RBCs: increased blood viscosity.

• Over 2 million RBCs produced per second.

Life Cycle of RBCs

• Life span: 100–120 days.

• RBCs are anucleate; cannot synthesize new proteins or divide.

• Old RBCs become fragile; hemoglobin degenerates.

• Trapped in spleen; macrophages engulf and break down dying RBCs.

• Iron stored for reuse; heme degraded to bilirubin (excreted in bile, further degraded in intestines).

• Globin metabolized to amino acids.

Regulation of Erythropoiesis

• Low O2 levels stimulate kidneys to produce erythropoietin (EPO).

• EPO and raw materials promote erythropoiesis in red bone marrow.

• New erythrocytes enter bloodstream; aged RBCs are removed by macrophages.

• Raw materials recycled for new RBC synthesis.

Disorders of Erythrocytes

Anemia

Anemia is a condition where blood has abnormally low O2-carrying capacity, insufficient for normal metabolism. Symptoms include fatigue, pallor, dyspnea, and chills.

• Blood Loss: Hemorrhagic anemia (rapid or chronic blood loss).

• Not Enough RBCs Produced: Iron-deficiency anemia (microcytes, small/pale RBCs), pernicious anemia (lack of intrinsic factor for B12 absorption, macrocytes), renal anemia (lack of EPO), aplastic anemia (destruction/inhibition of red bone marrow).

• Too Many RBCs Destroyed: Hemolytic anemias (incompatible transfusions, infections, genetic disorders).

Genetic Disorders

• Thalassemias: Faulty or absent globin chain; RBCs thin, delicate, deficient in hemoglobin.

• Sickle-cell anemia: Mutated hemoglobin S; RBCs become crescent-shaped under low O2, rupture easily, block vessels.

Polycythemia

• Abnormal excess of RBCs; increases blood viscosity, causing sluggish blood flow.

• Polycythemia vera: Bone marrow cancer; hematocrit may reach 80%.

• Secondary polycythemia: Caused by low O2 or increased EPO production.

• Blood doping: Athletes reinfuse RBCs to increase O2 for stamina.

Leukocytes (White Blood Cells)

General Structure and Function

• Only formed element that is a complete cell (with nuclei and organelles).

• Defense against disease; can leave capillaries via diapedesis.

• Move through tissue spaces by amoeboid motion and positive chemotaxis.

Classification of Leukocytes

• Granulocytes: Contain visible cytoplasmic granules.

  • Neutrophils: Most numerous; phagocytic; "bacteria slayers"; lobed nucleus.

  • Eosinophils: 2–4%; bilobed nucleus; role in allergies and asthma.

  • Basophils: 0.5–1%; contain histamine; similar to mast cells.

• Agranulocytes: No visible granules; spherical or kidney-shaped nuclei.

  • Lymphocytes: 15%; mostly in lymphoid tissues; crucial to immunity. T cells (virus/tumor defense), B cells (produce plasma cells).

  • Monocytes: Largest; 3–8%; differentiate into macrophages; fight viruses and chronic infection.

Leukopoiesis: Formation of WBCs

• Stimulated by interleukins and colony-stimulating factors.

• All leukocytes originate from hemocytoblast stem cells.

• Lymphoid stem cells produce lymphocytes; myeloid stem cells produce all other elements.

Leukocyte Disorders

• Leukemias: Cancerous overproduction of abnormal WBCs; named by cell type and progression (acute/chronic).

• Infectious mononucleosis: Viral disease (Epstein-Barr); high numbers of enlarged lymphocytes.

• Leukopenia: Abnormally low WBC count.

Platelets

Structure and Function

• Fragments of larger megakaryocytes; age quickly, degenerate in about 10 days.

• Form temporary platelet plug to seal breaks in blood vessels.

• Kept inactive by nitric oxide and prostacyclin.

• Regulated by thrombopoietin.

• Normal count: 150,000–400,000 platelets/μL blood.

Hemostasis

Steps of Hemostasis

1. Vascular Spasm: Vasoconstriction in response to injury; most effective in small vessels.

2. Platelet Plug Formation: Platelets stick to exposed collagen; activated platelets release ADP, serotonin, and thromboxane A2 (positive feedback cycle).

3. Coagulation: Reinforces platelet plug with fibrin threads; involves clotting factors (procoagulants).

Coagulation Pathways

• Intrinsic Pathway: Triggered by negatively charged surfaces (activated platelets, collagen, glass).

• Extrinsic Pathway: Triggered by tissue factor (TF) from outside blood.

• Both pathways lead to formation of prothrombin activator.

Phase 2: Prothrombin activator catalyzes transformation of prothrombin to thrombin.

Phase 3: Thrombin converts soluble fibrinogen to fibrin; fibrin forms structural basis of clot.

Thrombin (with Ca2+) activates fibrin stabilizing factor (factor XIII), cross-linking fibrin and stabilizing clot.

Clot Retraction and Fibrinolysis

• Actin and myosin in platelets contract, pulling fibrin strands and squeezing serum from clot.

• Platelet-derived growth factor (PDGF) stimulates vessel repair.

• Vascular endothelial growth factor (VEGF) restores endothelial lining.

• Fibrinolysis: Removal of clots after repair; plasminogen converted to plasmin (fibrin-digesting enzyme) by tissue plasminogen activator (tPA) and thrombin.

Disorders of Hemostasis

• Thromboembolic Disorders: Undesirable clot formation (thrombus, embolus, embolism).

• Bleeding Disorders: Abnormalities preventing normal clot formation (thrombocytopenia, hemophilia, disseminated intravascular coagulation).

Definitions

• Thrombus: Clot in unbroken vessel; may block circulation.

• Embolus: Thrombus floating in bloodstream.

• Embolism: Embolus obstructing vessel (e.g., pulmonary or cerebral emboli).

• Thrombocytopenia: Deficient platelets; causes spontaneous hemorrhage (petechiae).

• Hemophilia: Hereditary bleeding disorder; deficiency of clotting factors.

• Disseminated Intravascular Coagulation (DIC): Widespread clotting and severe bleeding.

Blood Groups and Transfusions

Blood Group Antigens

• RBC membranes bear antigens (agglutinogens).

• ABO blood groups based on presence/absence of A and B agglutinogens.

• Type A: A agglutinogen; Type B: B agglutinogen; Type AB: both; Type O: neither.

• Blood may contain preformed anti-A or anti-B antibodies (agglutinins).

Rh Blood Groups

• Rh+ indicates presence of D antigen.

• First exposure to Rh antigen: no response; second exposure: immune response (important in pregnancy).

Transfusing Red Blood Cells

• Whole-blood transfusions for rapid/substantial blood loss.

• Packed RBCs (plasma and WBCs removed) preferred to restore O2-carrying capacity.

• Blood banks separate blood into components; shelf life ~35 days.

Transfusion Reactions

• Donor cells attacked by recipient’s plasma agglutinins; agglutinate and clog vessels.

• Hemoglobin released into bloodstream; can cause renal failure.

Blood Typing and Cross Matching

• Donor blood mixed with antibodies against common agglutinogens; clumping indicates presence.

• Blood typed for ABO and Rh factor.

• Cross matching: recipient’s serum mixed with donor RBCs and vice versa.

Blood Group Table

Blood Group	Antigens	Antibodies	Blood That Can Be Received
A	A	Anti-B	A, O
B	B	Anti-A	B, O
AB	A and B	None	A, B, AB, O
O	None	Anti-A, Anti-B	O

Additional info: Rh+ individuals can receive Rh+ or Rh- blood; Rh- individuals should not receive Rh+ blood if previously sensitized.

Key Equations and Concepts

• Hematocrit: Percentage of blood volume that is RBCs.

• Osmotic Pressure: Maintained by plasma proteins, especially albumin.

• Hemoglobin Equation:

$\text{Hb} + \text{O}_2 \rightleftharpoons \text{HbO}_2$

$\text{Hb} + \text{CO}_2 \rightleftharpoons \text{HbCO}_2$

$\text{Hematocrit} = \frac{\text{Volume of RBCs}}{\text{Total Blood Volume}} \times 100\%$

Additional info: Normal hematocrit values: males 47% ± 5%, females 42% ± 5%.