9.1 Physiology of Blood

9.1 Physiology of Blood

Quick Answer: An adult's total blood volume is roughly 7% of body weight (about 70 mL/kg), split into ~55% plasma and ~45% formed elements. Red cells survive about 120 days, platelets 8-10 days, and neutrophils only hours in circulation. Red cells rely entirely on anaerobic glycolysis for ATP, and the resulting storage lesion (falling ATP and 2,3-DPG, rising extracellular potassium) directly shapes how specialists select and interpret blood components for exchange transfusion, massive transfusion, and neonatal support.

Blood Volume and Circulation

Total blood volume (TBV) is calculated differently across the lifespan, and a specialist must recognize these differences when evaluating transfusion volumes, exchange transfusion calculations, and apheresis procedures.

These values are the basis for calculating a double-volume exchange transfusion (2 x neonatal blood volume, or about 160 mL/kg) and for determining the maximum single-collection volume in apheresis donors. Blood is distributed roughly 70% in the venous system, 15% in the arterial system, and the remainder in capillaries and the pulmonary circulation at any given moment; this distribution explains why sudden blood loss is compensated first by venous constriction before arterial pressure falls.

Composition and Function of Blood

Whole blood separates into plasma (~55% of volume) and formed elements (~45% of volume, reported as the hematocrit). Plasma is approximately 91-92% water, about 7% proteins (albumin, globulins, fibrinogen, and other coagulation factors), and 1-2% other solutes (electrolytes, nutrients, waste products, hormones). Formed elements include:

• Erythrocytes (RBCs) - oxygen and carbon dioxide transport via hemoglobin
• Leukocytes (WBCs) - granulocytes (neutrophils, eosinophils, basophils) and mononuclear cells (lymphocytes, monocytes) for immune defense
• Platelets (thrombocytes) - primary hemostasis

Normal function depends on adequate numbers and activity of each cell line. Abnormal physiology includes anemia (reduced RBC mass or hemoglobin), polycythemia (increased RBC mass, raising blood viscosity and thrombosis risk), leukocytosis/leukopenia, and thrombocytosis/thrombocytopenia. Hypervolemia and hypovolemia are physiologic fluid states rather than cell-line disorders, and a specialist must distinguish true anemia from dilutional (hemodilutional) anemia after large-volume fluid resuscitation before recommending a transfusion.

Cell Survival

A transfused red cell unit near the end of its 42-day shelf life still contains cells with a full 120-day survival potential once in circulation; the storage lesion affects function and post-transfusion recovery at the time of transfusion, not the maximum theoretical lifespan of a surviving cell.

Cell Metabolism and the Storage Lesion

Mature erythrocytes have no nucleus and no mitochondria, so all ATP is produced through anaerobic glycolysis (the Embden-Meyerhof pathway), which accounts for roughly 90-95% of glucose use. About 5-10% of glucose is shunted through the hexose monophosphate (pentose phosphate) shunt, generating NADPH to protect hemoglobin and membrane lipids from oxidative damage (a pathway that fails in G6PD deficiency). A branch of glycolysis, the Rapoport-Luebering shunt, produces 2,3-diphosphoglycerate (2,3-DPG), which binds deoxyhemoglobin and shifts the oxygen dissociation curve to the right, promoting oxygen release to tissues.

During refrigerated storage (1-6 degrees C), red cells accumulate a predictable storage lesion:

• ATP and 2,3-DPG decline progressively
• Extracellular potassium rises as the membrane Na+/K+ pump slows
• pH falls as lactate accumulates
• Free hemoglobin and microparticles increase as some cells hemolyze

This lesion is clinically important for component therapy: 2,3-DPG depletion means a freshly transfused unit temporarily delivers oxygen less efficiently until levels regenerate over roughly 24-72 hours in vivo, and elevated extracellular potassium is a specific concern for rapid, large-volume transfusion in neonates (exchange transfusion, intrauterine transfusion) and in massive transfusion, where fresher or washed units are often specified. Irradiation, required to prevent transfusion-associated graft-versus-host disease in intrauterine and neonatal exchange settings, accelerates potassium leakage further, reinforcing why those specific components must also be as fresh as possible before issue.

Relevance to Component Therapy and Apheresis

Blood volume and composition principles are not academic background; they drive concrete transfusion-medicine calculations. Estimated blood volume determines the maximum safe single collection during therapeutic or donor apheresis (procedures generally limit extracorporeal volume to a small percentage of total blood volume to avoid hypotension), and the same TBV estimate is used to calculate expected post-transfusion hemoglobin or hematocrit rise from a given component volume. Recognizing normal cell survival also explains post-transfusion recovery expectations: a properly stored, viable red cell unit should show at least 75% 24-hour in vivo recovery by regulatory standard, after which surviving transfused cells continue to age normally toward the full 120-day lifespan. Understanding abnormal physiology, such as polycythemia vera raising blood viscosity, or third-spacing and iatrogenic fluid overload producing dilutional anemia, allows a specialist to correctly distinguish patients who need therapeutic phlebotomy or careful transfusion pacing from those who need red cell replacement, and to recognize transfusion-associated circulatory overload (TACO) as a volume-driven complication rather than a true immune reaction.