Human Physiology: Blood and Extracellular Fluids

Extracellular Fluids of the Body

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

Blood: Composition and Function

• Blood is a connective tissue with formed elements (cells) in a liquid extracellular matrix (plasma).
• Blood accounts for ~8% of body mass.
• Average male blood volume: 5-6 L; average female: 4-5 L.
• Blood is more viscous than water.
• Blood temperature: ~38ºC; pH: 7.35-7.45.
• Three main functions:
  • Transportation (oxygen, nutrients, hormones, heat, waste)
  • Regulation (pH, body temperature, osmotic pressure)
  • Protection (against blood loss, invasion, disease)

Composition of Blood

• Two components:
  • Blood plasma (55%):
    • Liquid extracellular matrix containing dissolved substances (91.5% water, 8.5% solutes).
    • Proteins: albumin (maintains osmotic pressure), globulins (antibodies, transport proteins), fibrinogen (blood clotting).
    • Other solutes: electrolytes, nutrients, enzymes, hormones, gases, metabolic wastes.
  • Formed elements (45%):
    • Erythrocytes (red blood cells): most abundant, transport O2 and CO2. Lack organelles at maturity to maximize space for hemoglobin.
    • Leukocytes (white blood cells): various types, fight infection and invasion.
    • Platelets (thrombocytes): cell fragments, crucial for clotting.

Blood Cell Formation (Hemopoiesis)

• Blood cells are continuously replenished.
• Hemopoiesis occurs in red bone marrow.
• Starts from pluripotent stem cells.
• Develops into two lineages: myeloid stem cells and lymphoid stem cells.
• Each lineage produces precursor cells that differentiate into formed elements.
• WBCs divide after leaving bone marrow.

Regulation of Blood Cell Formation

• Hematopoietic growth factors (hormones affecting blood cell formation):
  • Erythropoietin (EPO): increases erythrocyte production, produced in kidneys.
  • Thrombopoietin (TPO): stimulates platelet formation, produced in the liver.
  • Cytokines: stimulate leukocyte and lymphocyte proliferation, produced in red bone marrow.

Erythrocytes (Structure and Function)

• Biconcave discs: large surface area to volume ratio, flexible for capillary passage.
• Anucleate at maturity; lack most organelles except for hemoglobin (Hb).
• Hb transports oxygen (~250 million Hb/erythrocyte).
• Also carry ~23% of body's CO2.
• Contain carbonic anhydrase: converts CO2 to carbonic acid (important blood buffer).
• Nitric oxide (NO) acts as a hormone, released by endothelial cells in response to stress, causing vasodilation.
• Life span: ~120 days.
• Worn-out erythrocytes are destroyed by macrophages in the liver, spleen, or red bone marrow.

Erythrocyte Life Cycle

• Hemoglobin broken down; globin into amino acids (recycled); iron (ferric) bound to transferrin, stored in ferritin or transported to bone marrow for new erythropoiesis.
• Iron-less heme products: yellow products excreted by kidneys, others in feces.
• Erythropoiesis is stimulated by reduced oxygen transport (hypoxia) via EPO.

Leukocytes (Structure and Function)

• Granular leukocytes: neutrophils, eosinophils, basophils (contain visible granules).
• Agranular leukocytes: lymphocytes (derived from lymphoid stem cells), monocytes (derived from myeloid stem cells, differentiate into macrophages).
• Major functions: infection and invasion defense.

Leukocyte Function: Inflammation and Immunity

• WBCs defend against infection, express MHC proteins (self-identifying).
• Invaders trapped, cilia sweep away debris.
• WBCs accumulate at infection site (emigration), chemotaxis.
• Neutrophils: fast responders, phagocytize pathogens, release lysozyme, oxidizing chemicals, defensins.
• Eosinophils: fight parasites, secrete histaminase to disrupt signaling.
• Basophils: inflammatory and hypersensitivity reactions, release heparin, histamine, serotonin.
• Lymphocytes: circulate and reside in lymphatic system, B lymphocytes produce antibodies, T lymphocytes and natural killer cells fight infected and cancerous cells.
• Monocytes: differentiate into wandering macrophages, clean up cell debris.
• Inflammation leads to emigration, chemotaxis, tissue disinfection, and tissue healing.

Platelets

• Formed from megakaryocytes which divide themselves into fragments that are now platelets.
• Contain granules with clotting factors.
• Life span: 5-9 days.

Hemostasis

• Hemostasis prevents excessive bleeding:
  • Vascular spasm: blood vessel damage causes smooth muscle spasm
  • Platelet plug formation: platelets adhere, activate, aggregate (clumping).
  • Blood clotting (coagulation): platelet plug + insoluble protein fibers for reinforcement.

Blood Clot Formation

• Clotting factors (including Ca2+, liver-made enzymes, platelet substances): intrinsic (internal damage) and extrinsic (external factor) pathways.
• Activation of factor X leads to formation of prothrombinase from factor X and V which then converts prothrombin to thrombin.
• Thrombin acts on fibrinogen converting it into fibrin.
• Factor XIII stabilizes fibrin threads.

Blood Clotting Regulation

• Tightly controlled: thrombosis (clumping) = blocked vessels, emboli (embolism) = stroke, pulmonary embolism; hemorrhage (excessive bleeding) = anemia, shock.

Diseases and Disorders of Blood

• ABO blood groups: glycolipid antigens; agglutinins (antibodies) clump erythrocytes (agglutination), individuals make antibodies against foreign antigens.
• Hemolytic Disease of the Newborn (HDN): Rh factor incompatibility between mother and fetus.
• Anemia: reduced oxygen carrying capacity (many causes).
• Sickle cell disease: genetic mutation in globin gene, elongated cells, protects against malaria.
• Hemophilia: insufficient clotting factors.
• Polycythemia: too many erythrocytes, thickened blood.