Blood and the Cardiovascular System: Structure, Function, and Disorders

Blood Composition and Plasma

Plasma: Structure and Function

Blood plasma is a straw-colored, sticky fluid that forms the liquid component of blood. It is composed mostly of water but contains over 100 dissolved solutes, including gases, hormones, and electrolytes. Electrolytes are the most abundant solutes in plasma.

• Plasma Proteins: Produced mainly by the liver, these proteins are not used as fuel by cells. The most abundant plasma protein is albumin (about 60%), which acts as a carrier, a blood buffer, and is crucial for maintaining plasma osmotic pressure (keeping water in the bloodstream).

Formed Elements of Blood

Types and Characteristics

The formed elements of blood include erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. Only leukocytes are complete cells; erythrocytes lack nuclei and most organelles, and platelets are cell fragments. Most formed elements survive only a few days in the bloodstream and are replaced by stem cells in the bone marrow.

Erythrocytes (Red Blood Cells)

Structure and Function

Erythrocytes are specialized for transporting respiratory gases (oxygen and carbon dioxide). Mature erythrocytes are biconcave, lack a nucleus, and contain no organelles, making them highly efficient oxygen transporters. They are essentially bags of hemoglobin and some antioxidant enzymes.

• Hemoglobin: A protein that binds easily and reversibly with oxygen. Each hemoglobin molecule consists of four polypeptide chains (two alpha and two beta), each with a heme group containing an iron atom. Each iron atom can bind one oxygen molecule, so one hemoglobin can carry four oxygen molecules.

• Efficiency: Erythrocytes lack mitochondria and generate ATP anaerobically, so they do not consume the oxygen they transport.

Hemoglobin and Oxygen Transport

Each red blood cell contains about 250 million hemoglobin molecules, allowing each cell to carry approximately 1 billion oxygen molecules. When oxygen binds to hemoglobin, it forms oxyhemoglobin (ruby red); when oxygen detaches, it becomes deoxyhemoglobin (dark red).

Erythrocyte Production (Erythropoiesis)

Blood cell formation, or hematopoiesis, occurs in red bone marrow. The process from hematopoietic stem cell to reticulocyte takes about 15 days, with full maturation occurring 2 days after entering the bloodstream.

Regulation of Erythropoiesis

Erythropoiesis is regulated hormonally by erythropoietin (EPO), a glycoprotein hormone produced mainly by the kidneys (and to a lesser extent, the liver). EPO stimulates red blood cell production in response to hypoxia (low oxygen levels).

Fate and Destruction of Erythrocytes

Erythrocytes have a lifespan of 100–120 days. As they age, they become fragile and are removed from circulation, primarily by macrophages in the spleen. The iron from hemoglobin is salvaged and reused, the heme group is converted to bilirubin, and the globin is broken down into amino acids.

Erythrocyte Disorders

• Anemia: A condition where the blood's oxygen-carrying capacity is too low, leading to fatigue, pallor, shortness of breath, and chills. Causes include blood loss, insufficient red blood cell production, or excessive destruction of red blood cells.

• Low Production: Can result from iron deficiency (microcytic anemia), vitamin B12 deficiency (pernicious anemia), lack of EPO (renal anemia), or bone marrow failure (aplastic anemia).

• Destruction: Hemolytic anemia (rupture of erythrocytes), sickle-cell anemia (abnormal hemoglobin causing cell rupture and vessel blockage).

Leukocytes (White Blood Cells)

Types and Functions

Leukocytes are less numerous than erythrocytes but are crucial for defense against disease. They are complete cells with nuclei and organelles and can leave the bloodstream to enter tissues (diapedesis). There are two main categories: granulocytes and agranulocytes.

• Granulocytes: Neutrophils, eosinophils, basophils (contain visible cytoplasmic granules).

• Agranulocytes: Lymphocytes, monocytes (lack visible granules).

Granulocytes

• Neutrophils: Most abundant, multilobed nucleus, phagocytic, "bacteria slayers."

• Eosinophils: Bilobed nucleus, red-staining granules, attack parasitic worms, modulate immune response.

• Basophils: Rarest, large granules containing histamine, involved in inflammatory responses.

Agranulocytes

• Lymphocytes: Large, dark nucleus, crucial for immunity. T cells act against infected/tumor cells; B cells produce antibodies.

• Monocytes: Largest leukocytes, U- or kidney-shaped nucleus, differentiate into macrophages in tissues, phagocytic.

Leukopoiesis

Leukopoiesis is the production of white blood cells, stimulated by interleukins and colony-stimulating factors (CSFs). All leukocytes originate from hemocytoblasts in the bone marrow.

Leukocyte Disorders

• Leukopenia: Abnormally low WBC count, often drug-induced.

• Leukemias: Cancers involving overproduction of abnormal WBCs, classified by cell type and progression (acute or chronic).

• Infectious Mononucleosis: Viral disease (Epstein-Barr virus) with high numbers of atypical agranulocytes.

Platelets

Structure and Function

Platelets are cytoplasmic fragments of megakaryocytes, essential for blood clotting. They form temporary plugs to seal vessel breaks and are regulated by thrombopoietin. Platelets age quickly and are replaced every 10 days.

Summary Table: Formed Elements of the Blood

Cell Type	Description	Cells/μL	Life Span	Function
Erythrocytes	Biconcave, anucleate	4.2–6.1 million	100–120 days	Transport oxygen and carbon dioxide
Neutrophils	Multilobed nucleus, pale granules	3,000–7,000	6 hours–few days	Phagocytize bacteria
Eosinophils	Bilobed nucleus, red granules	100–400	~5 days	Kill parasitic worms, modulate allergies/asthma
Basophils	Bilobed nucleus, large granules	20–50	~few hours–few days	Release histamine, mediate inflammation
Lymphocytes	Large nucleus, thin rim cytoplasm	1,500–3,000	Hours–years	Mount immune response
Monocytes	Kidney-shaped nucleus	100–700	Months	Phagocytosis, develop into macrophages
Platelets	Cell fragments	150,000–400,000	5–10 days	Seal small tears, blood clotting

Hemostasis

Steps in Hemostasis

Hemostasis is the process of stopping bleeding and involves 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 release chemicals to attract more platelets (positive feedback).

3. Coagulation: Reinforcement of the platelet plug with fibrin threads, transforming blood from liquid to gel.

Coagulation Pathways

Coagulation involves a cascade of reactions with clotting factors:

• Intrinsic Pathway: Triggered by factors within the blood (e.g., activated platelets, collagen).

• Extrinsic Pathway: Triggered by tissue factor from outside the blood (damaged endothelium).

• Both pathways converge at factor X, leading to the formation of prothrombin activator, conversion of prothrombin to thrombin, and transformation of fibrinogen to fibrin.

Clot Retraction and Vessel Repair

After clot formation, platelets contract to pull the wound edges together (clot retraction). Platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) stimulate repair of the vessel wall and endothelium.

Fibrinolysis

Fibrinolysis removes unneeded clots after healing. Plasminogen is converted to plasmin, which digests fibrin and dissolves the clot.

Disorders of Hemostasis

• Thromboembolic Disorders: Formation of undesirable clots (thrombus, embolus, embolism).

• Bleeding Disorders: Abnormalities that prevent normal clot formation, such as thrombocytopenia (low platelet count) and hemophilia (deficiency of clotting factors).

Human Blood Groups and Transfusions

ABO Blood Groups

Red blood cell membranes have glycoprotein antigens (agglutinogens) that determine blood type. The presence or absence of A and B antigens classifies blood into four groups: A, B, AB, and O. Mismatched transfusions can cause agglutination and hemolysis, which may be fatal.

Transfusion Reactions

Transfusion reactions occur if mismatched blood is infused, leading to agglutination, hemolysis, and potentially kidney failure. Symptoms include fever, chills, low blood pressure, and rapid heartbeat. Treatment focuses on preventing kidney damage by flushing out hemoglobin.

Complete Blood Count (CBC)

A CBC measures the counts and characteristics of different blood cells, including WBCs, RBCs, hemoglobin, hematocrit, and platelets. It is a key diagnostic tool in clinical medicine.