Blood and Extracellular Fluids Overview

Extracellular Fluids

• Three extracellular fluids: blood, interstitial fluid, and lymph
• Nutrients travel from blood to interstitial fluid to cells.

Blood Overview

• Blood is formed elements (cells) in a liquid extracellular matrix (ECM) called blood plasma.
• Blood circulates in the cardiovascular system (blood, blood vessels, heart).
• Hematology is the study of blood and blood-forming tissues.
• Blood accounts for 8% of body mass.
• Average male blood volume: 5-6 liters; average female: 4-5 liters.
• Blood is more viscous (thick) than water.
• Blood temperature: ~38ºC; pH range: 7.35-7.45.
• Three main functions:
  • Transportation: oxygen, nutrients, hormones, heat, waste.
  • Regulation: pH, body temperature, osmotic pressure.
  • Protection: blood loss, disease.

Blood Composition

• Two components:
  • Blood plasma (55%): liquid ECM with dissolved substances.
  • Formed elements (45%): erythrocytes, leukocytes, platelets.

Blood Plasma

• Pale yellow liquid, 91.5% water, 8.5% solutes.
• Proteins:
  • Albumin (54%): maintains osmotic pressure.
  • Globulins (38%): antibodies, transport proteins.
  • Fibrinogen (7%): blood clotting.
• Other solutes: electrolytes, nutrients, enzymes, hormones, gases, metabolic wastes.

Formed Elements

• Three main components:
  • Erythrocytes (red blood cells): most abundant, transport O2 and CO2. Mature cells lack organelles.
  • Leukocytes (white blood cells): diverse types, fight infection and invasion.
  • Platelets (thrombocytes): cell fragments, involved in clotting.

Hematocrit

• Hematocrit: percentage of blood volume occupied by erythrocytes.
• Normal adult range: ~47%.
• Low hematocrit (<40) can result in anemia.
• High hematocrit (>65) can increase risk of blood clots.

Blood Cell Formation (Hemopoiesis)

• Continuous process in red bone marrow.
• Starts with pluripotent stem cells.
• Two lineages: myeloid and lymphoid stem cells.
• Each stem cell produces precursor cells that differentiate into formed elements.
• Only WBCs divide after leaving the marrow.

Blood Cell Formation Regulation

• Hematopoietic growth factors regulate blood cell formation.
• Erythropoietin (EPO): increases erythrocyte precursor production, kidney-derived.
• Thrombopoietin (TPO): stimulates platelet formation, liver-derived.
• Cytokines: stimulate leukocyte and lymphocyte proliferation, marrow-derived.

Erythrocytes (Structure & Function)

• Biconcave discs: large surface area for gas exchange.
• Anucleate: no nucleus for maximum hemoglobin (Hb) space.
• Hb transports oxygen.
• Lack mitochondria for more Hb space.
• Adult females: ~4.8 million erythrocytes/μL; adult males: ~5.4 million erythrocytes/μL.

Erythrocyte Function in Gas Transport

• Hb reversibly binds up to four oxygen molecules.
• Erythrocytes transport ~23% of carbon dioxide.
• Erythrocytes contain carbonic anhydrase, which converts CO2 to carbonic acid to bicarbonate, forming a buffer system.
• Nitric oxide (NO) acts as a hormone, released by endothelial cells in response to cardiac stretch. NO binds Hb, leading to vasodilation.

Erythrocyte Life Cycle

• ~120 days.
• Erythrocytes die from wear and tear through capillaries; inability to repair.
• Macrophages destroy worn-out or damaged RBCs in the liver, spleen, or marrow.
• Globin (organic) and heme (inorganic) separated.
• Globin recycled into amino acids.
• Ferric iron (Fe3+) from heme bound to transferrin (Fe transport protein) and shuttled through liver.
• Fe3+ from heme stored in ferritin.
• Iron reattached to transferrin,carried to marrow for erythropoiesis.
• Hemoglobin-less heme products removed by the liver/kidneys/feces.

Erythropoiesis

• Tightly controlled process.
• Hypoxia (low oxygen to tissues) triggers erythropoiesis.
• Kidneys detect hypoxia, release EPO.
• EPO stimulates proerythroblasts to mature faster.
• Results in more erythrocytes for oxygen delivery.

Leukocytes (Structure & Function)

• All organelles present, no hemoglobin.
• Granular or agranular.
• Granular have vesicles: neutrophils, eosinophils, basophils.
• Agranular: lymphocytes, monocytes.

Granular Leukocytes

• Neutrophils: phagocytic, have multi-lobed nuclei (polymorphonuclear). Defend against bacteria through phagocytosis and killing mechanisms.
• Eosinophils: defend against parasites, have bilobed nuclei.
• Basophils: involved in inflammatory and hypersensitivity reactions, have bilobed nuclei. Release histamine, heparin, and serotonin.

Agranular Leukocytes

• Lymphocytes: derived from lymphoid stem cells, diverse in size. Increased large lymphocytes indicate disease.
• Monocytes: derived from myeloid stem cells, differentiate into macrophages (or fuse into osteoclasts), clean up debris.

Leukocyte Function: Inflammation and Immunity

• WBCs defend against infection and invasion.
• Express MHC (major histocompatibility complex) proteins (self).
• Mucous membranes trap invaders; cilia sweep them away.
• WBCs emigrate (leave bloodstream) from infection site.
• WBCs locate infection via chemotaxis.
• Neutrophils are rapid responders; phagocytize pathogens. Release lysozyme, oxidizing chemicals, and defensins to kill bacteria.
• Eosinophils fight parasitic infections, secrete histaminase (breaks down histamine).
• Monocytes differentiate into wandering macrophages, clean up cellular debris.
• Inflammation is a response to tissue damage, which involves WBC emigration, chemotaxis, disinfection, and healing.

Platelets

• Form from megakaryocytes splitting into fragments.
• Granules with clotting chemicals.
• 5-9 day lifespan.

Hemostasis

• Prevents excessive bleeding (hemorrhage).
• Three steps: vascular spasm, platelet plug formation, blood clotting.

Vascular Spasm

• Damaged vessels constrict, limiting bleeding.

Platelet Plug Formation

• Platelets adhere to vessel injury, activate and release granules. ADP makes platelets sticky, resulting in aggregation (clumping).

Blood Clot Formation

• Reinforces platelet plug with insoluble protein fibers.
• Coagulation involves clotting factors, including calcium (Ca2+), liver-made enzymes (proenzymes), platelet, and tissue substances.

Blood Clotting Pathways

• Intrinsic pathway: triggered within blood vessels by contact with collagen.
• Extrinsic pathway: triggered by tissue factor (TF) from damaged vessel cells.
• Common pathway follows intrinsic/extrinsic activation (uses factor X, V, prothrombinase, thrombin, fibrinogen, fibrin & factor XIII).

Blood Clotting Regulation

• Prevents inappropriate clotting (thrombosis, embolus).
• Prevents excessive bleeding (hemorrhage).
• Uncontrolled clotting can lead to stroke or pulmonary embolism.

Blood Groups

• ABO blood groups based on glycolipid antigens in erythrocyte membranes.
• Agglutinins (antibodies) bind to foreign antigens, causing agglutination (clumping).
• Individuals make antibodies against foreign antigens (e.g. O type produces anti-A and anti-B antibodies).

Hemolytic Disease of the Newborn (HDN)

• Rh factor (protein antigen) on erythrocytes. Rh-negative mothers can develop anti-Rh antibodies if exposed to Rh-positive fetus.
• First child unaffected; subsequent Rh-positive children at risk for HDN.
• Anti-Rh antibodies cross placenta, agglutinate fetal erythrocytes, causing fetal damage.
• Treated proactively with anti-Rh gamma globulin (RhoGAM).

Other Homeostatic Imbalances

• Anemia: low erythrocyte count, various causes.
• Sickle-cell disease: genetic mutation, abnormal hemoglobin, sickle-shaped cells, resistance to malaria due to potassium leakage from cells.
• Hemophilia: insufficient clotting factors.
• Polycythemia: excess erythrocytes, thick blood, risk of stroke, emboli.