3.1 – Formed Elements of the Blood

Composition of Blood & “Formed Elements”

• Blood = plasma (fluid) + formed elements (cells/cell fragments).
• Formed elements (focus of this video):
• Erythrocytes (RBCs) — pale-pink discs, overwhelmingly most abundant.
• Leukocytes (WBCs) — immune cells; much rarer; several subclasses.
• Platelets (thrombocytes) — tiny cell fragments critical for clotting; usually not obvious on histology smear.
• Governing Objectives covered: Unit 3 Objectives 2-4.

Hematopoiesis (General)

• Definition: production of all blood cells; occurs in red bone marrow.
• Starts from “pluripotent” hematopoietic stem cell (HSC).
• First bifurcation →
• Myeloid stem cell → erythrocytes, megakaryocytes (→ platelets), and 4 of the 5 leukocyte types.
• Lymphoid stem cell → lymphocytes (T cells, B cells, NK cells).
• Conceptual mnemonic: “career path” of a stem cell steadily narrows as it differentiates.

Erythrocytes (Red Blood Cells)

Structure & Functional Anatomy

• Smallest human blood cells, diameter ≈ 7\,\text{µm}.
• Biconcave disk: concave surfaces on both sides.
• ↓ internal volume; ↑ surface-area-to-volume ratio → faster O2 diffusion.
• Anucleate & no mitochondria (lose both during maturation) → frees space for hemoglobin; prevents RBCs from consuming the O2 they transport.

Hemoglobin (Hb)

• Main cytoplasmic protein; gives blood its red color.
• Quaternary structure: 4 globin chains, each bound to a heme group.
• Each heme centers an Fe^{2+} ion → binds O2 reversibly.
• \text{1 Hb} = 4\,\text{O}_2 \text{ max}.

Hematocrit (Hct)

• Operational definition: \text{Hct} = \dfrac{\text{volume of RBCs}}{\text{total blood volume}} \times 100\%.
• Measured by centrifugation (≈ 10 000\,\text{rpm}):
• Bottom → dense RBC layer.
• Thin buffy coat in middle → WBCs + platelets.
• Top → plasma.
• Typical values (from diagram):
• Males \approx 47\% (±5\%).
• Females \approx 42\% (±5\%).

Clinical Significance of Hematocrit & RBC Count

• Low Hct → various anemias; etiologies include iron deficiency, impaired erythropoiesis, blood loss.
• High Hct
• Acute: dehydration.
• Physiologic: chronic high altitude (e.g., athletes training at altitude; Sherpas). Persisting effect ≈ weeks.
• Pathologic: polycythemia (→ ↑ blood viscosity, ↑ BP).

Erythropoiesis & Its Regulation

• Sub-branch of hematopoiesis (myeloid line).
• Hormone Erythropoietin (EPO) — secreted mainly by kidneys, lesser by liver.
• Stimuli for EPO release:
• Hypoxia (↓ arterial \text{O}_2; high altitude, pulmonary disease).
• ↓ Plasma volume (dehydration, hemorrhage, diuretics).
• Stem-cell defects.
• Negative feedback loop (homeostasis review — Lectures 11/03 & 11/09):

  1. Hypoxia → kidneys release EPO.
  2. EPO → red marrow ↑ rate of erythropoiesis.
  3. ↑ RBC count & Hb → ↑ blood \text{O}_2-carrying capacity.
  4. Restored \text{O}_2 inhibits further EPO secretion.

Leukocytes (White Blood Cells)

General Features

• ≈ 0.1\% of total blood cells (visually the buffy coat is ~/1000 thickness of RBC layer).
• All possess a nucleus (stains purple).
• Function: defense; operate in blood, lymph, and tissues → many actively exit capillaries (diapedesis).

Leukocyte Categories & Microscopic ID

• Granulocytes (prominent cytoplasmic granules)

  1. Neutrophils
    • Multi-lobed “string-of-beads” nucleus.
    • Function: phagocytose bacteria/fungi; secrete antimicrobial chemicals.
    • “Single-use” → very abundant (most common leukocyte).
  2. Eosinophils
    • Large red/orange granules; bi-lobed nucleus often obscured.
    • Anti-inflammatory & anti-parasitic (kills worms with toxic proteins).
    • Normally rare.
  3. Basophils
    • Dark purple-black granules.
    • Release histamine & other pro-inflammatory mediators; lowest normal count.
    • Agranulocytes (lack visible granules)
  4. Lymphocytes (T cells, B cells, NK cells)
    • Small; huge spherical nucleus occupying most cytoplasm.
    • Central players of adaptive immunity (covered next week).
  5. Monocytes
    • Largest leukocyte; kidney- or U-shaped nucleus.
    • Exit blood → differentiate into macrophages; long-lived, repeated phagocytosis.

Differential WBC Count (Clinical Tool)

• Lab quantifies % distribution of 5 WBC types; deviations suggest etiology.
• ↑ Basophils → allergic reactions, hyperthyroidism.
• ↑ Eosinophils → parasitic worm infection, allergic asthma.
• ↑ Neutrophils → acute bacterial infection, burns.
• ↓ Lymphocytes (especially T cells) → AIDS (HIV targets T cells).

Leukopoiesis

• Two branches:
• Myeloid stem cell lineage → granulocytes + monocytes.
• Lymphoid stem cell lineage → lymphocytes.
• Regulated by colony-stimulating factors (CSFs) & other cytokines, often secreted by existing leukocytes (“calling for reinforcements”).

Platelets (Thrombocytes)

• Not true cells — membrane-bound fragments of megakaryocytes (myeloid lineage).
• Primary function: initiate hemostasis (clot formation); details in clotting lecture.

Blood Viscosity Determinants

• Directly proportional to two key variables:
• Hematocrit (RBC mass).
• Plasma albumin concentration (most abundant plasma protein).
• Higher viscosity → ↑ peripheral resistance → ↑ blood pressure.

Cross-Lecture Connections & Conceptual Threads

• Stem cell concepts refer back to embryology/cell differentiation (Lecture 11/09).
• Membrane diffusion, surface-area-to-volume ratio, and organelle loss revisit cell bio principles (Lecture 11/03).
• Negative feedback & hormonal control echo endocrine/homeostasis topics.
• Adaptive immunity (T/B cells) and cytokine signaling preview upcoming immune-system lectures.
• High-altitude erythropoiesis ties physiology to real-world phenomena (athletic training, Sherpa adaptation).
• Ethical/clinical lens: EPO doping in sports; managing polycythemia; transfusion medicine based on hematocrit.