Week 1: Blood Composition and Hematopoiesis

Circulatory & Cardiovascular System Overview

• Circulatory system = heart + blood vessels + blood (liquid medium)
  • When only heart + vessels are considered → cardiovascular system.
• Fundamental goal: transport substances between body regions.
• Closely integrated with the respiratory system (lungs exchange gases that blood then distributes).
• Study of blood = hematology.

Functions of Blood

• Transportation
  • O$2$ from lungs → tissues; CO$2$ from tissues → lungs.
  • Nutrients from digestive tract, hormones from endocrine glands, metabolic wastes to excretory organs.
  • Heat redistribution.
• Regulation
  • Homeostasis of fluid volume & distribution.
  • pH stabilization via multiple buffer systems (normal arterial pH 7.35\text{–}7.45).
  • Thermoregulation (blood temp ≈ 38\;^\circ\text{C} / 100.4\;^\circ\text{F}, slightly above core body temperature).
• Protection
  • Inflammation containment & mediation.
  • Immune surveillance/destruction of pathogens (leukocytes, antibodies, complement).
  • Hemostasis: platelet plug formation, coagulation cascade → clot (fibrin framework) to minimize blood loss.

Composition of Blood

• Total volume in adults ≈ 4\text{–}6\;\text{L}
  • Males 5\text{–}6\;\text{L}; females 4\text{–}5\;\text{L}.
• Two major components:
  1. Plasma (liquid ECM) ≈ 55\% of volume.
  2. Formed elements (cells & fragments) ≈ 45\% of volume.

Blood Plasma

• Clear, light-yellow fluid (density < formed elements).
• Composition
  • Water (≈ 92\%) – solvent for transport & heat distribution.
  • Proteins (most synthesized by liver) – highest impact on viscosity/osmolarity.
  • Nutrients: glucose, amino acids, lipids, vitamins.
  • Electrolytes: Na$^+$, Cl$^-$, K$^+$, Ca$^{2+}$, etc.
  • Gases: O$2$, CO$2$, N$_2$.
  • Nitrogenous wastes: urea, uric acid, creatinine.

Major Plasma Proteins

• Albumin (≈ 60\% of plasma proteins)
  • Functions: transports lipids, hormones, electrolytes; buffers pH.
  • Viscosity & Osmolarity
  • Hyperalbuminemia → high viscosity (sluggish flow) + high osmolarity → water enters blood ⇒ ↑ volume & ↑ BP.
  • Hypoalbuminemia → low viscosity (rapid flow) + low osmolarity → water stays in tissues ⇒ ↓ volume & ↓ BP, edema.
  • Clinical causes
  • Hyperalbuminemia: dehydration, excessive water loss.
  • Hypoalbuminemia: liver/kidney failure, severe burns, dietary protein deficiency.
• Globulins (≈ 36\%)
  • Subclasses: α-globulins & β-globulins (transport lipids, minerals, hormones, Hb from dead RBCs); γ-globulins (antibodies for adaptive immunity).
• Fibrinogen (≈ 4\%)
  • Soluble precursor → fibrin (insoluble) during coagulation → clot framework.
  • Elevated fibrinogen ↑ viscosity → possible ↑ BP.
  • Plasma minus fibrinogen = serum.

Formed Elements

• Erythrocytes (RBCs)
  • Contain hemoglobin (Hb) for O$2$ & CO$2$ transport.
  • Densest component; settle at bottom in centrifuge.
• Leukocytes (WBCs)
  • Immunologic defense; coordinate tissue-damage responses.
  • Five main types: neutrophils, eosinophils, basophils, monocytes, lymphocytes.
• Thrombocytes (Platelets)
  • Cell fragments from megakaryocytes; key role in clotting.

Physical & Chemical Characteristics of Whole Blood

• Viscosity: higher than water due to cells & proteins.
• Density: greater than water.
• Color: bright red when oxygenated; dark red (maroon) when deoxygenated.

Blood Fractionation & Hematocrit

• Centrifugation layers (top → bottom):
  1. Plasma (lightest) \approx 47\text{–}63\%.
  2. Buffy coat (WBCs + platelets) \approx 1\%, cream-colored.
  3. Erythrocytes: 37\text{–}52\%; percentage = hematocrit (packed cell volume).
• Hematocrit importance: indicator of O$_2$-carrying capacity & hydration status.

Hematopoiesis

• Daily production: ≈ 400\text{×}10^9 platelets, 200\text{×}10^9 RBCs, 10\text{×}10^9 WBCs.
• Sites (hematopoietic tissues)
  • Fetal: yolk sac → liver, spleen, thymus, bone marrow.
  • Post-natal: red bone marrow primary site (sternum, ribs, skull, pelvis, vertebrae, epiphyses of femur/humerus/tibia).
• Hematopoietic stem cells (HSCs) / pluripotent stem cells (PSCs)
  • Pluripotent = capable of multiple lineages.
  • Two primary progenitor lines:
  1. Myeloid stem cells → RBCs, platelets, neutrophils, eosinophils, basophils, monocytes.
  2. Lymphoid stem cells → lymphocytes (B, T, NK cells).

Regulatory Growth Factors

• Erythropoietin (EPO) – \approx 85\% kidneys, 15\% liver; stimulates erythropoiesis.
• Colony-Stimulating Factors (CSFs) – drive leukopoiesis.
• Thrombopoietin (TPO) – liver & kidneys; stimulates thrombopoiesis (megakaryocyte → platelets).

Specific Lines of Hematopoiesis

• Erythropoiesis: HSC → myeloid stem cell → erythrocyte lineage; regulated by EPO (↑ when tissue hypoxia detected).
• Leukopoiesis: HSC → myeloid or lymphoid stem cells → diverse WBCs; regulated by CSFs.
• Thrombopoiesis: HSC → myeloid stem cell → megakaryocyte → fragmentation → platelets; regulated by TPO.

Clinical Correlations & Pathologies

• Liver failure → ↓ plasma protein synthesis → hypoalbuminemia → edema, hypotension.
• Dehydration → hyperalbuminemia & relative polycythemia (↑ hematocrit).
• Severe burns → protein loss → hypoalbuminemia; management requires high-protein diet + fluid resuscitation.
• Elevated fibrinogen → ↑ blood viscosity & BP; risk factor for thrombosis.
• Hematocrit shifts
  • ↑ Hematocrit (polycythemia) may result from hypoxia, EPO doping.
  • ↓ Hematocrit (anemia) from blood loss, nutritional deficiency, marrow failure.

Summary & Key Takeaways

• Blood = plasma (water + solutes + proteins) + formed elements (RBCs, WBCs, platelets).
• Major proteins: albumin (transport, pH, osmolarity), globulins (transport, immunity), fibrinogen (coagulation).
• Formed elements derived from HSCs in red bone marrow via hematopoiesis; regulated hormonally (EPO, CSFs, TPO).
• Plasma minus clotting proteins = serum.
• Centrifugation separates blood by density: plasma → buffy coat → RBCs; hematocrit quantifies RBC fraction.
• Proper protein balance essential for blood viscosity, osmolarity, and overall cardiovascular health.