Chapter 19: Blood – Structure, Function, and Clinical Relevance

Blood: Structure and Function

Functions of Blood

Blood is a vital connective tissue that performs essential functions for organismal homeostasis. Its roles include transport, protection, and regulation:

• Transport and Distribution:

  • Transports oxygen (O2) from lungs to body cells.

  • Removes carbon dioxide (CO2) from cells to lungs for exhalation.

  • Delivers nutrients from the digestive system to tissues.

  • Transports hormones from endocrine glands to target cells.

  • Distributes metabolic heat throughout the body.

• Protection:

  • Prevents blood loss via platelets and clotting factors (hemostasis).

  • Defends against infection using leukocytes (white blood cells) and antibodies.

• Regulation:

  • Maintains fluid and ion balance by transferring water (H2O) between blood and tissues.

  • Regulates blood pH by transporting acids and bases; blood acts as a reserve for bicarbonate ions (HCO3-).

  • Stabilizes body temperature and blood pressure.

General Characteristics of Blood

Blood possesses unique physical and chemical properties that support its functions:

• Viscosity: Blood is more dense than water due to the presence of formed elements (cells and cell fragments). This affects its flow and the workload of the heart.

• pH: Slightly alkaline, ranging from 7.35 to 7.45.

• Temperature: Approximately 100°F (38°C).

• Volume: Depends on body mass; typically 5–6 liters in males, 4–5 liters in females.

• Estimation Formula: Blood volume (in liters) ≈ 7% of body weight in kilograms. Conversion: 1 kg = 2.2 lbs.

Example: A 70 kg adult has an estimated blood volume of 4.9 liters.

Components of Whole Blood

Blood consists of two main components:

• Formed Elements:

  • Cells: Red blood cells (RBCs, erythrocytes), white blood cells (WBCs, leukocytes).

  • Cell Fragments: Platelets (thrombocytes).

• Plasma: The yellowish extracellular fluid that serves as the dissolving and suspending medium for blood solutes. Plasma composition changes with cellular activity and carries heat.

Blood Plasma: Proteins and Other Constituents

Plasma contains several types of proteins and solutes:

• Albumin (60% of plasma proteins):

  • Maintains blood pH (buffer).

  • Major determinant of plasma osmotic pressure (oncotic pressure).

  • Transports substances such as hormones and drugs.

• Globulins:

  • Gamma globulins (immunoglobulins): Antibodies for immune response.

  • Alpha and beta globulins: Transport hormones, lipids, and fat-soluble vitamins.

• Clotting Proteins (4%):

  • Fibrinogen: Forms the basic framework for blood clots.

• Other Plasma Constituents:

  • Electrolytes: Na+, K+, Ca2+, Cl-, HCO3-

  • Nutrients: Glucose, amino acids, fatty acids, cholesterol, vitamins.

  • Waste products: Lactic acid, urea, uric acid, bilirubin.

  • Blood gases: Oxygen (O2), carbon dioxide (CO2).

Plasma Expanders

Plasma expanders are used to temporarily increase blood volume in cases of hypovolemia (low blood volume):

• Isotonic Saline Solution (0.9% NaCl): Prevents cell shrinkage (crenation) or bursting (hemolysis).

• Lactated Ringer's Solution: Contains lactate ions, prolongs expansion effect.

• Colloids (e.g., Dextran, Mannose): Protein or carbohydrate-based solutions used in clinical settings for longer-lasting volume expansion.

Additional info: Plasma expanders do not carry oxygen; only red blood cells do.

Formed Elements: Overview

The formed elements of blood include:

• Erythrocytes (RBCs): Specialized for gas transport.

• Leukocytes (WBCs): Responsible for immune defense.

• Thrombocytes (Platelets): Cell fragments essential for hemostasis (blood clotting).

Blood cells do not divide; they are replenished by hematopoiesis in red bone marrow.

Hematopoiesis

Hematopoiesis is the process of blood cell formation and differentiation:

• Begins around the third week of embryonic development.

• Sites: Liver, spleen, bone marrow (in adults: axial skeleton, proximal epiphyses of femur and humerus).

• All blood cells arise from hematopoietic stem cells (HSCs), which differentiate into specific cell types via colony forming units (CFUs).

• Regulated by hormones and growth factors.

Erythrocytes: Structure and Function

Red blood cells are highly specialized for oxygen and carbon dioxide transport:

• Shape: Biconcave disc, flexible, large surface-to-volume ratio for rapid gas exchange.

• Organelles: Lack most organelles; rely on anaerobic glycolysis for energy.

• Hemoglobin (Hb): Abundant protein that binds O2 and CO2 reversibly.

  • Oxyhemoglobin: Hb + O2

  • Carbaminohemoglobin: Hb + CO2

  • Deoxyhemoglobin: Hb without O2

Hematocrit: Percentage of blood volume occupied by RBCs (avg. 46% in males, 42% in females).

Hemoglobin Structure

Hemoglobin is a globular protein composed of four subunits:

• Adult hemoglobin (HbA): 2 alpha and 2 beta chains.

• Each subunit contains a heme group with an iron (Fe2+) atom that binds O2.

• Each hemoglobin molecule can carry up to 4 O2 molecules.

Gas Exchange Basics

Oxygen and carbon dioxide are exchanged between blood and tissues:

• In lungs: O2 diffuses into plasma and RBCs, binds hemoglobin (bright red blood).

• In tissues: O2 dissociates from hemoglobin, diffuses out (dull red blood).

Fetal Hemoglobin and Other Variants

• Fetal hemoglobin (HbF): 2 alpha and 2 gamma chains; higher affinity for O2 than adult Hb.

• Carboxyhemoglobin: Hb binds carbon monoxide (CO), reducing O2 transport (smoking risk).

• Glycated hemoglobin (HbA1c): Used to monitor average blood glucose over 3 months.

Erythropoiesis

Formation of RBCs requires amino acids, iron, vitamin B12, and folic acid:

• Regulated by erythropoietin (EPO), released by kidneys in response to hypoxia.

• Negative feedback increases RBC production during anemia, hemorrhage, or high altitude.

• Blood doping artificially increases RBC count (EPO injections, transfusions).

Erythrocyte Turnover

Damaged RBCs are phagocytized by macrophages in bone marrow:

• Hemoglobin is broken down into amino acids and iron.

• Iron is recycled or stored as ferritin/hemosiderin in liver and bone marrow.

• Heme is converted to biliverdin (green), then bilirubin (yellow), transported to liver and excreted in bile.

• Bacteria in the intestine convert bilirubin to stercobilin (feces) and urobilin (urine).

Erythrocyte Disorders

• Anemia: Reduced oxygen-carrying capacity due to decreased RBCs, hemoglobin, or abnormal Hb.

  • Types: Aplastic, hemolytic, iron deficiency, sickle cell.

  • Symptoms: Pallor, fatigue, weakness, cardiac and nervous system dysfunction.

• Sickle Cell Disease: Inherited mutation in beta-globin gene; abnormal Hb-S polymerizes under stress, distorting RBCs and causing hemolytic anemia.

• Pernicious Anemia: Macrocytic anemia due to vitamin B12 deficiency (impaired DNA synthesis).

• Polycythemia: Excess RBCs increase blood viscosity and risk of vessel occlusion.

Leukocytes: Types and Functions

White blood cells are complete cells involved in immune defense:

• Neutrophils (50–70%): Phagocytic, target bacteria, contain hydrolytic enzymes and defensins.

• Lymphocytes (30%): Found in lymphoid tissues; include T cells (cell-mediated immunity), B cells (antibody production), and natural killer cells.

• Monocytes (4–8%): Largest WBCs; differentiate into macrophages, phagocytic.

• Eosinophils (2–4%): Defend against parasites, involved in allergic reactions.

• Basophils (1%): Release histamine and heparin, enhance inflammation, involved in allergic responses.

Leukopoiesis: Formation of WBCs, regulated by interleukins and colony stimulating factors.

Thrombocytes (Platelets)

Platelets are cell fragments essential for hemostasis:

• Form temporary plugs at injury sites.

• Secrete vasoconstrictors and clotting factors.

• Regulated by thrombopoietin, interleukin-6, and multi-CSF.

Hemostasis: Blood Clotting

Hemostasis is the process of stopping blood loss after injury:

1. Vascular Phase: Vasoconstriction limits blood loss; endothelial cells release endothelins and von Willebrand factor (vWF).

2. Platelet Phase: Platelets adhere to exposed collagen, become activated, release ADP, Ca2+, thromboxane A2, and serotonin.

3. Coagulation Phase: Formation of a fibrin clot via intrinsic and extrinsic pathways.

4. Clot Retraction: Fibrin contracts, pulling wound edges together.

5. Thrombolysis: Clot is dissolved by plasmin after tissue repair.

Clotting Factors: Main Purpose and Table

Clotting factors are proteins and enzymes essential for coagulation. They are classified by Roman numerals and have specific roles in the clotting cascade.

Factor	Name	Function
I	Fibrinogen	Forms fibrin threads
II	Prothrombin	Converted to thrombin
III	Tissue Factor	Initiates extrinsic pathway
IV	Calcium ions	Cofactor in all pathways
V	Proaccelerin	Accelerates prothrombin activation
VIII	Antihemophilic factor	Intrinsic pathway; deficiency causes hemophilia A
IX	Christmas factor	Intrinsic pathway; deficiency causes hemophilia B
X	Stuart-Prower factor	Common pathway activation
Additional info:	Other factors (VI, VII, XI, XII, XIII)	Roles in various steps of the cascade

Coagulation Pathways

• Intrinsic Pathway: Initiated by contact with negatively charged surfaces (e.g., exposed collagen); slower, involves Factors XII, XI, IX, VIII.

• Extrinsic Pathway: Initiated by tissue factor (Factor III) from damaged tissue; rapid, involves Factor VII.

• Common Pathway: Begins with activation of Factor X; forms prothrombinase, converts prothrombin to thrombin, which converts fibrinogen to fibrin.

Key Equations:

• Prothrombinase catalyzes: $\text{Prothrombin} \xrightarrow{\text{Prothrombinase}} \text{Thrombin}$

• Thrombin catalyzes: $\text{Fibrinogen} \xrightarrow{\text{Thrombin}} \text{Fibrin}$

Factors Limiting Clot Growth

• Prostacyclin inhibits platelet aggregation.

• Enzymes in plasma break down ADP.

• Thrombin binds to fibrin strands, limiting its spread.

Thrombolysis

After healing, clots are dissolved by the fibrinolytic system:

• Tissue plasminogen activator (tPA) converts plasminogen to plasmin.

• Plasmin degrades fibrin, dissolving the clot.

Blood Type: ABO and Rh Systems

Blood type is determined by antigens on erythrocyte membranes:

• ABO System:

  • Type A: A antigen, anti-B antibody in plasma.

  • Type B: B antigen, anti-A antibody in plasma.

  • Type AB: Both A and B antigens, no anti-A/B antibodies.

  • Type O: No A/B antigens, both anti-A and anti-B antibodies.

• Rh (D) Antigen: Presence (+) or absence (–) determines Rh status.

Transfusion Reactions: Occur when recipient antibodies agglutinate donor erythrocytes.

Clinical Perspectives

• Blood tests are crucial for diagnosing disease and monitoring health.

• Abnormalities in blood composition or delivery can have profound consequences.

• Hemostasis is essential for survival, limiting blood loss after injury.

Exercise and Blood Volume

Chronic exercise increases blood volume:

• Plasma volume expands first (within 24 hours), due to increased renin, angiotensin II, and ADH.

• Albumin synthesis increases plasma osmolarity, shifting fluid into blood.

• Erythrocyte volume expands over weeks, increasing oxygen-carrying capacity and VO2max.

Example: After >21 days of exercise, VO2max increases by ~16% due to increased erythrocyte volume.

Disorders of Hemostasis

• Thromboembolic Disorders: Clots form in unbroken vessels (thrombus); can travel (embolus) and block smaller vessels (embolism).

• Bleeding Disorders: Liver dysfunction, vitamin K deficiency, or inherited clotting factor deficiencies (e.g., hemophilia) impair hemostasis.

Leukemia

Leukemia is a cancer of blood or bone marrow, characterized by excessive production of abnormal WBCs:

• Acute: Rapid increase in immature cells.

• Chronic: Gradual increase over years.

• Lymphocytic: Affects lymphoid stem cells.

• Myelocytic: Affects myeloid stem cells.

Acute Myelocytic Leukemia (AML): Linked to smoking, chemical exposure, prior chemotherapy, and radiation. Treated with chemotherapy, bone marrow transplant; 5-year survival rate varies.

Summary Table: Blood Cell Types and Functions

Cell Type	Main Function	Key Features
Erythrocyte	O2/CO2 transport	Biconcave, no nucleus, hemoglobin-rich
Neutrophil	Phagocytosis (bacteria)	Multi-lobed nucleus, granules
Lymphocyte	Immunity (T/B/NK cells)	Large nucleus, little cytoplasm
Monocyte	Phagocytosis (macrophage)	Kidney-shaped nucleus
Eosinophil	Parasite defense, allergy	Bilobed nucleus, red granules
Basophil	Inflammation, allergy	S-shaped nucleus, dark granules
Platelet	Hemostasis	Cell fragment, no nucleus

Additional info: For more on blood color chemistry, see: compoundchem.com/2014/10/28/coloursofblood/