Ch 17 Blood System Notes: Plasma, Erythrocytes, Hematopoiesis, and Leukocytes

Plasma and Formed Elements

  • Blood is composed of formed elements and a liquid plasma. The formed elements are erythrocytes (RBCs), leukocytes (WBCs), and platelets. RBCs and platelets are not true cells in some sense: platelets are fragments of a megakaryocyte plasma membrane, and RBCs lack nuclei and most organelles.

  • The liquid portion (plasma) makes up about 55% of blood. By volume, plasma is mostly water, with small amounts of plasma proteins and electrolytes.

  • Plasma water content: approximately 92\%\sim93\% of plasma is water.

  • Plasma proteins are a key constituent and account for about 8% of plasma by weight; the remainder varies with body conditions (water vs protein content) and electrolytes.

  • The term “constituents” includes everything present in plasma other than water and plasma proteins; there is some variability in exact percentages depending on conditions.

  • The most abundant plasma protein is albumin, making up about 60\% of plasma proteins. Albumin is produced by the liver and is the main contributor to osmotic (oncotic) pressure, helping to keep fluids in the bloodstream and regulating fluid balance.

  • Globulins constitute about 36\% of plasma proteins and are divided into:

    • Alpha and beta globulins, produced by the liver, serving primarily as transport proteins for lipids, metal ions, and fat-soluble vitamins.

    • Gamma globulins, produced by plasma cells, which are antibodies.

  • Fibrinogen is another major plasma protein produced by the liver; it polymerizes to form fibrin threads during blood clotting.

  • Nonprotein nitrogenous wastes present in plasma include urea, uric acid, ammonium, and ammonia, produced as byproducts of cellular metabolism of proteins.

  • Nutrients circulate in plasma and are transported to tissues; energy sources include carbohydrates, lipids, and proteins. Nucleic acids are not used directly for energy.

  • Electrolytes are also present in plasma and vary with physiology and conditions.

Erythrocytes (Red Blood Cells) and Hemoglobin

  • Erythrocytes are disc-shaped (biconcave) cells that are larger than some capillaries. They possess spectrin protein that allows them to fold and regain shape after passing through narrow vessels.

  • The biconcave shape provides a high surface area-to-volume ratio, which facilitates efficient gas exchange (CO2 out, O2 in).

  • Red blood cells lack mitochondria and rely on anaerobic glycolysis; they do not use the oxygen they carry.

  • Lifespan of erythrocytes is typically about 70\sim120\text{ days}, with variation between individuals.

  • Hemoglobin (Hb) inside each RBC carries oxygen. Each RBC contains about 2.5\times10^8 Hb molecules, and each Hb molecule can bind up to 4 O2 molecules.

    • Therefore, the total oxygen-carrying capacity per RBC is approximately
      (2.5\times10^8)\times 4 = 1.0\times10^9
      oxygen molecules per RBC.

  • The presence of oxygen on hemoglobin is referred to as oxyhemoglobin (bright red); when oxygen is released, it becomes deoxyhemoglobin (dark red).

  • A small fraction of CO2 is transported bound to hemoglobin as carbaminohemoglobin (CO2 attached to Hb); the major CO2 transport is not on hemoglobin.

Erythrocyte Formation (Hematopoiesis) and Lineage

  • Erythrocyte formation occurs in red bone marrow (hematopoiesis).

  • The stem cell lineage starts with a hematopoietic stem cell (hemocytoblast) that can become a myeloid stem cell and subsequently commit to erythrocyte formation.

  • Key stages and terminology (order reflects maturation):

    • Hematopoietic stem cell (hemocytoblast) → myeloid stem cell → proerythroblast (committed to erythrocyte lineage)

    • Basophilic erythroblast (ribosome synthesis; beginning Hb production; color shifts toward reddish as Hb increases)

    • Orthochromatic erythroblast (most organelles and nucleus are removed; cell becomes biconcave in preparation for circulation)

    • Erythrocyte (released into circulation; maturation period from proerythroblast to erythrocyte is on the order of about 14\sim15\text{ days}, often rounded to ~2 weeks)

  • The process relies on reticular tissue in the marrow, with reticular fibers forming a scaffold that resembles shelves for cell development.

  • All three formed elements (RBCs, WBCs, platelets) arise from the same hematopoietic stem cell, though they follow distinct lineages as they mature.

  • Regulation of RBC production involves erythropoietin (EPO): hypoxia (low blood oxygen) stimulates the kidneys to secrete EPO, which targets red bone marrow to increase RBC production.

  • Location details in adults: red bone marrow is located at the ends of long bones; the medullary cavity in the shafts contains yellow marrow (fat) and does not actively produce RBCs under normal adult conditions.

  • The RBC production cycle also requires essential nutrients and factors: amino acids, lipids, carbohydrates; vitamin B12 and folic acid are critical for rapid RBC synthesis; intrinsic factor from stomach cells is required to absorb B12.

    • B12 deficiency or intrinsic factor deficiency leads to pernicious anemia (autoimmune destruction of intrinsic factor-producing cells impairs B12 absorption).

    • Iron is essential for hemoglobin; iron transport and storage are tightly regulated.

Iron Metabolism and Storage

  • Iron in the body is transported in the blood bound to transferrin for delivery to tissues and developing RBCs.

  • Iron is stored intracellularly as ferritin or hemosiderin.

  • The body requires iron for hemoglobin synthesis; insufficient iron can reduce Hb production and contribute to anemia.

Nutritional and Regulatory Requirements for RBC Production

  • B12 (cobalamin) and folic acid (vitamin B9) are essential for RBC synthesis; intrinsic factor (stomach-derived) is required to absorb B12. Absence of intrinsic factor leads to impaired B12 absorption and pernicious anemia.

  • Iron is needed for heme synthesis; is transported by transferrin and stored as ferritin/hemosiderin.

  • RNA and ribosome synthesis during erythroblast stages (basophilic erythroblast) contributes to Hb production, influencing the color changes observed during maturation.

Erythrocyte Disorders and Clinical Context

  • Anemia refers to too few red blood cells or insufficient hemoglobin.

  • Hemorrhagic anemia results from acute or chronic blood loss; symptoms are usually temporary after stabilization.

  • Pernicious anemia is an autoimmune condition where loss of intrinsic factor impairs B12 absorption, leading to defective RBC production.

  • Renal (kidney) anemia occurs when kidneys fail to produce adequate erythropoietin (EPO).

  • Aplastic anemia involves bone marrow suppression or destruction, reducing production of all formed elements (RBCs, WBCs, platelets); treatment may involve stem cell transplantation.

  • Thalassemia is characterized by defective or missing hemoglobin chains, leading to fragile RBCs and reduced Hb content; often associated with Mediterranean populations.

  • Sickle cell anemia requires two recessive gene copies; RBCs become crescent-shaped under low-oxygen conditions, leading to vascular occlusion and reduced oxygen delivery. Carriers (one recessive allele) may have some protective advantages in malaria-endemic regions.

  • Blood doping and EPO use increase RBC counts and hematocrit, raising oxygen-carrying capacity but risking dangerous hyperviscosity, thrombosis, stroke, and heart attack. Hematocrit can rise from typical values around 45% to as high as 65%; dehydration can worsen this risk by decreasing plasma volume.

  • The regulatory and ethical implications of therapies (e.g., transfusions, EPO doping, stem cell transplantation, and emerging immune therapies) require careful consideration of risks, benefits, and long-term outcomes.

White Blood Cells (Leukocytes) and Blood Chemistry

  • White blood cells are the only formed elements that are complete cells (they have nuclei and organelles).

  • WBCs can be categorized as:

    • Granulocytes: contain granules in the cytoplasm. Subtypes include neutrophils, eosinophils, and basophils.

    • Agranulocytes: lack cytoplasmic granules. Subtypes include lymphocytes and monocytes.

  • The mnemonic never let monkeys eat bananas helps recall the relative order used in some teaching contexts: Neutrophils (N), Lymphocytes (L), Monocytes (M), Eosinophils (E), Basophils (B).

  • Percentages of circulating leukocytes (typical ranges):

    • Neutrophils: 50\%\sim70\%

    • Lymphocytes: 20\%\sim40\%

    • Monocytes: 3\%\sim8\%

    • Eosinophils: 2\%\sim4\%

    • Basophils: 0.5\%\sim1\%

  • The relative low percentages of eosinophils and basophils in normal blood often reflect specific immune states (e.g., parasitic infection elevates eosinophils; significant allergic inflammation raises basophils). The exact counts can vary and zero or near-zero values may be observed in healthy individuals.

  • The next class session will cover the individual white blood cell types in more detail.

Real-World and Ethical Contexts Mentioned

  • Vaccines and immune memory: vaccines aim to generate memory cells so that subsequent exposures trigger faster, stronger responses; effectiveness can vary with viral variants, and booster shots may be needed.

  • Viral latency and reactivation: Varicella-zoster virus can cause chickenpox initially and reappear later as shingles; immune status affects the risk of reactivation.

  • Immunotherapies: advanced approaches like T-cell therapies (e.g., CAR-T concepts) engineer immune cells to target cancers; this illustrates the broader theme of how immune system manipulation can treat disease.

  • The balance between medical advances and risks: therapies like stem cell transplantation or erythropoietic stimulation require careful consideration of benefits, risks, and potential complications.

Quick Reference: Key Numerics and Terms

  • RBC lifespan: 70\sim120\ \text{days}

  • Hematopoietic flow to erythrocyte: proerythroblast → basophilic erythroblast → orthochromatic erythroblast → erythrocyte (two-week scale timing)

  • RBC oxygen-carrying capacity per cell: N{Hb} \approx 2.5\times10^8\;\Rightarrow\; N{O2,RBC} = N_{Hb}\times 4 \approx 1.0\times10^9 molecules of O2

  • Hematocrit ranges and changes with doping: typical baseline around ~45\%; with doping potential increases to ~65\% (dangerous increases in blood viscosity)

  • Iron transport/storage: transferrin (transports), ferritin/ hemosiderin (stores)

  • Key factors for RBC production: amino acids, lipids, carbohydrates; Vitamin B12 and folate; intrinsic factor required for B12 absorption

  • Major plasma proteins: Albumin (≈60% of plasma proteins; liver-produced; maintains osmotic pressure), Globulins (≈36%; alpha/beta liver-produced; gamma antibodies), Fibrinogen (liver-produced; clot formation)

End of notes

  • If you need, I can convert these into a condensed study sheet with a smaller number of bullets for quick review, or expand any section with diagrams or step-by-step flowcharts.