Blood: Composition, Function, and Hemostasis

Blood: Composition, Function, and Hemostasis

Overview of Blood Circulation

Blood is a vital fluid connective tissue that circulates throughout the body, delivering oxygen and nutrients while removing waste products. It travels through two main circuits: the systemic circuit (delivering blood to the body) and the pulmonary circuit (delivering blood to the lungs for oxygenation).

• Systemic Circuit: Blood exits the heart via arteries, which branch into capillaries for exchange of gases and nutrients. Oxygen-deficient blood returns to the heart through veins.

• Pulmonary Circuit: Blood is pumped from the heart to the lungs for oxygenation and then returns to the heart to be distributed to the body.

Blood Composition

Blood consists of a liquid matrix called plasma and formed elements (cells and cell fragments) suspended within it. When blood is centrifuged, it separates into three distinct layers:

• Plasma: The top layer, comprising about 55% of blood volume, is a straw-colored fluid containing water, proteins, nutrients, hormones, and waste products.

• Buffy Coat: A thin middle layer (<1%) containing leukocytes (white blood cells) and platelets.

• Erythrocytes: The bottom layer (about 45%), consisting of red blood cells, which are the most dense component.

Physical Characteristics and Volume

Blood is a sticky, opaque fluid with a metallic taste. Its color varies with oxygen content (scarlet when oxygen-rich, dark red when oxygen-poor). Blood is more viscous than water, has a pH of 7.35–7.45, and constitutes about 8% of body weight. Average blood volume is 5–6 L for males and 4–5 L for females.

Functions of Blood

• Distribution: Transports oxygen, nutrients, hormones, carbon dioxide, and metabolic wastes.

• Regulation: Maintains body temperature, pH balance, and fluid volume.

• Protection: Prevents blood loss through clotting and combats infection via immune cells.

Blood Plasma

Composition of Plasma

Plasma is about 90% water and contains over 100 dissolved solutes, including:

• Nutrients, gases, hormones, wastes, proteins, and electrolytes.

• Plasma Proteins: Most abundant solutes, produced mainly by the liver.

  • Albumin (60%): Maintains osmotic pressure, acts as a buffer, and transports substances.

  • Globulins (36%): Alpha and beta globulins transport lipids and fat-soluble vitamins; gamma globulins function as antibodies.

  • Fibrinogen (4%): Essential for blood clotting.

Formed Elements

Types of Formed Elements

The formed elements of blood include erythrocytes (RBCs), leukocytes (WBCs), and platelets. Most are short-lived and originate in the bone marrow.

• Erythrocytes (RBCs): Anucleate, biconcave discs specialized for oxygen transport.

• Leukocytes (WBCs): Complete cells involved in immune defense.

• Platelets: Cell fragments essential for blood clotting.

Erythrocytes (Red Blood Cells)

Erythrocytes are biconcave, anucleate cells filled with hemoglobin for gas transport. Their shape increases surface area for efficient gas exchange and allows flexibility to pass through capillaries.

• Structure: Biconcave disc, no nucleus or organelles, contains spectrin for flexibility.

• Function: Dedicated to respiratory gas transport; hemoglobin binds reversibly with oxygen.

• Normal Values: Males: 13–18 g/100 ml; Females: 12–16 g/100 ml hemoglobin.

Hemoglobin Structure and Function

Hemoglobin (Hb) is the protein responsible for oxygen transport in the blood. Each molecule consists of four polypeptide chains (two alpha, two beta) and four heme groups, each containing an iron atom that binds one oxygen molecule.

• Oxyhemoglobin: Hemoglobin bound to oxygen (lungs; bright red).

• Deoxyhemoglobin: Hemoglobin after oxygen release (tissues; dark red).

• Carbaminohemoglobin: Hemoglobin bound to carbon dioxide (tissues).

Hematopoiesis and Erythropoiesis

Hematopoiesis

Hematopoiesis is the process of blood cell formation, occurring primarily in red bone marrow. All formed elements arise from hematopoietic stem cells (hemocytoblasts).

• Locations: Axial skeleton, girdles, and proximal epiphyses of humerus and femur in adults.

• Stem Cells: Hemocytoblasts differentiate into various blood cells under hormonal and growth factor control.

Erythropoiesis: Red Blood Cell Production

Erythropoiesis is the specific process of RBC production. It involves several stages, from myeloid stem cell to mature erythrocyte, and is regulated by the hormone erythropoietin (EPO).

• Stages: Myeloid stem cell → proerythroblast → basophilic erythroblast → polychromatic erythroblast → orthochromatic erythroblast → reticulocyte → erythrocyte.

• Regulation: EPO is released by the kidneys in response to hypoxia (low oxygen levels), stimulating RBC production.

• Dietary Requirements: Iron, vitamin B12, folic acid, amino acids, and other nutrients are essential for erythropoiesis.

Fate and Destruction of Erythrocytes

RBCs have a lifespan of 100–120 days. Old or damaged RBCs are removed by macrophages in the spleen, liver, and bone marrow. Hemoglobin is broken down, and its components are recycled or excreted.

• Iron: Salvaged and stored for reuse.

• Heme: Degraded to bilirubin, excreted in bile as stercobilin (brown pigment in feces).

• Globin: Broken down into amino acids for reuse.

Erythrocyte Disorders

Anemia

Anemia is a condition characterized by a decreased oxygen-carrying capacity of the blood. It is a sign of an underlying disorder rather than a disease itself.

• Causes:

  • Blood loss (hemorrhagic anemia)

  • Low RBC production (iron-deficiency, pernicious, renal, aplastic anemia)

  • High RBC destruction (thalassemias, sickle-cell anemia)

• Symptoms: Fatigue, pallor, shortness of breath, chills.

Polycythemia

Polycythemia is an abnormal excess of erythrocytes, leading to increased blood viscosity and impaired circulation.

• Polycythemia vera: Bone marrow cancer causing excessive RBC production.

• Secondary polycythemia: Result of low oxygen availability (e.g., high altitude) or increased EPO production.

• Blood doping: Artificially induced polycythemia to enhance athletic performance, with significant health risks.

Leukocytes (White Blood Cells)

Types and Functions

Leukocytes are crucial for immune defense and are classified as granulocytes or agranulocytes based on the presence of cytoplasmic granules.

• Granulocytes: Neutrophils, eosinophils, basophils.

• Agranulocytes: Lymphocytes, monocytes.

Neutrophils

• Most numerous WBCs; phagocytize bacteria and fungi.

• Granules stain lilac; nucleus has 3–6 lobes.

Eosinophils

• 2–4% of WBCs; combat parasitic worms, modulate immune response, and contribute to allergies and asthma.

• Bilobed nucleus; red-staining granules.

Basophils

• Rarest WBCs; release histamine for inflammation and attract other WBCs.

• Large, purplish-black granules; nucleus with 1–2 constrictions.

Lymphocytes

• Second most numerous WBC; crucial for immunity.

• T cells attack infected/tumor cells; B cells produce antibodies.

Monocytes

• Largest WBCs; differentiate into macrophages in tissues.

• Phagocytize pathogens and activate lymphocytes.

Leukopoiesis

Leukopoiesis is the production of WBCs, stimulated by interleukins and colony-stimulating factors (CSFs). All leukocytes originate from hematopoietic stem cells.

Platelets and Hemostasis

Platelets

Platelets are cytoplasmic fragments derived from megakaryocytes. They play a critical role in blood clotting by forming temporary plugs at sites of vessel injury.

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

• Regulated by thrombopoietin.

Hemostasis

Hemostasis is the process of stopping bleeding through a series of rapid, localized reactions involving platelets and clotting factors. It consists of three main steps:

1. Vascular Spasm: Vasoconstriction of damaged blood vessels to reduce blood loss.

2. Platelet Plug Formation: Platelets adhere to exposed collagen fibers, become activated, and aggregate to form a plug.

3. Coagulation: A cascade of reactions converts fibrinogen to fibrin, forming a stable blood clot.

Coagulation Cascade

The coagulation cascade involves a series of enzymatic reactions leading to the formation of a fibrin mesh that stabilizes the platelet plug. The process is divided into three phases:

1. Phase 1: Formation of prothrombin activator (requires clotting factors and Ca2+).

2. Phase 2: Conversion of prothrombin to thrombin.

3. Phase 3: Conversion of fibrinogen to fibrin.

Factor Number	Factor Name	Nature	Source	Pathway/Function
I	Fibrinogen	Plasma protein	Liver	Converted to fibrin in common pathway
II	Prothrombin	Plasma protein	Liver	Converted to thrombin in common pathway
IV	Calcium ions (Ca2+)	Inorganic ion	Diet	Required for all stages of coagulation
VIII	Antihemophilic factor (AHF)	Plasma protein	Liver, lung, capillaries	Intrinsic pathway; deficiency results in hemophilia A
XIII	Fibrin stabilizing factor	Plasma protein	Liver, bone marrow	Cross-links fibrin, stabilizing clot
Additional info: Table abbreviated for key factors; see full table for all factors.

Clot Retraction, Vessel Repair, and Fibrinolysis

• Clot Retraction: Platelets contract, pulling fibrin strands together and drawing wound edges closer.

• Vessel Repair: Platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) stimulate healing.

• Fibrinolysis: Removal of unneeded clots by plasmin, which digests fibrin.

Disorders of Hemostasis

Thromboembolic Disorders

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

• Embolus: Freely floating clot; can cause embolism if it lodges in a vessel.

Bleeding Disorders

• Thrombocytopenia: Low platelet count, leading to spontaneous bleeding.

• Hemophilia: Hereditary deficiency of clotting factors, causing prolonged bleeding.

Transfusions and Blood Groups

Human Blood Groups

Blood groups are determined by the presence or absence of specific antigens (agglutinogens) on RBC membranes. The most clinically important are the ABO and Rh groups.

• ABO System: Four types (A, B, AB, O) based on A and B antigens.

• Rh System: Presence (+) or absence (–) of Rh antigen (D antigen).

Transfusion Reactions

If incompatible blood is transfused, the recipient's antibodies attack donor RBCs, causing agglutination and hemolysis, which can be fatal. Blood typing and cross-matching are essential before transfusion.

Hemolytic Disease of the Newborn (Erythroblastosis Fetalis)

Occurs when an Rh– mother carries an Rh+ fetus. Maternal anti-Rh antibodies can cross the placenta and destroy fetal RBCs in subsequent pregnancies. Prevention involves administration of RhoGAM to the mother.

Diagnostic Blood Tests and Developmental Aspects

Diagnostic Blood Tests

• Hematocrit: Measures RBC percentage; used to diagnose anemia.

• Blood Glucose: Assesses diabetes.

• WBC Count: Indicates infection, allergy, or parasitic infection.

• Platelet Count: Assesses hemostasis.

• Complete Blood Count (CBC): Comprehensive evaluation of formed elements and hemoglobin.

Developmental Aspects

• Fetal blood cells form in the yolk sac, liver, and spleen before red bone marrow becomes the primary site.

• Fetal hemoglobin (HbF) has a higher affinity for oxygen than adult hemoglobin (HbA).

• Blood diseases in aging include chronic leukemias, anemias, and clotting disorders, often secondary to other systemic diseases.