11.1 Physiology of Blood

11.1 Physiology of Blood

Quick Answer: Adult blood volume is about 70 mL/kg. Red cells live about 120 days; platelets about 8–10 days. Oxygen delivery depends on hemoglobin, 2,3-DPG, and the Bohr effect. Refrigerated storage lowers 2,3-DPG and ATP and raises extracellular potassium — the storage lesion. Anemia is low red-cell mass; hypovolemia is low circulating volume. Issue red cells for inadequate oxygen-carrying capacity; use volume expanders when the problem is volume, not hemoglobin.

This is June 9, 2026 outline III.B.1. It is physiology that explains why a unit works, not the manufacturing clocks in Chapter 4 or the therapy thresholds in Chapter 17. If a stem asks blood volume, cell survival, oxygen unloading, storage lesion, or transfusion versus crystalloid, answer it here.

Blood volume and what is in the bag

Adult circulating volume is about 70 mL/kg — roughly 5 L in a 70 kg adult. Men sit a little higher, women a little lower. Neonates are closer to 80–90 mL/kg, which is why a 15 mL/kg pediatric red-cell dose is a larger fraction of their volume than one adult unit is of yours. Plasma volume is about 40 mL/kg; red-cell mass about 25–30 mL/kg. At a normal hematocrit, whole blood is about 55% plasma and 45% cells.

Three formed elements matter at the transfusion bench:

• Red cells are anucleate, hemoglobin-packed oxygen carriers. Adult hemoglobin A is α2β2. One additive-solution unit raises a stable ~70 kg adult’s hemoglobin about 1 g/dL and hematocrit about 3% (Chapter 4.1). That increment is a property of the dose, not a reason to transfuse.
• Plasma is water, albumin, globulins, coagulation factors, and electrolytes. Oncotic pressure is mostly albumin. Plasma is the starting material for FFP, PF24, and cryoprecipitate, not a red-cell substitute.
• Platelets are megakaryocyte fragments. The reference interval is about 150–450 × 10^9/L. They form the primary plug and provide phospholipid for thrombin generation.

Leukocytes are not a transfusion goal except a directed granulocyte product. They are why inventory is leukoreduced.

A 70 kg adult who loses 500 mL has lost about 10% of circulating volume. Immediately after an acute bleed, hematocrit can still look almost normal because cells and plasma left together. Dilution appears after interstitial fluid or crystalloid refill the space. That timing is why a “normal hematocrit in the trauma bay” does not mean the patient is not bleeding.

Oxygen delivery — hemoglobin, 2,3-DPG, Bohr

Tissue oxygen delivery is cardiac output × arterial oxygen content. Arterial content is almost entirely 1.34 mL O2 × hemoglobin (g/dL) × saturation, plus a negligible dissolved term. Cardiac output can compensate for a lower hemoglobin until it cannot. That is the physiologic reason a euvolemic patient at 7 g/dL may be stable and a bleeding patient at 9 g/dL may not.

The oxyhemoglobin dissociation curve decides unloading at the capillary:

• 2,3-DPG binds deoxyhemoglobin and decreases oxygen affinity (right shift) so tissues receive oxygen. Fresh cells have abundant 2,3-DPG.
• Bohr effect: rising PCO2 and falling pH right-shift the curve. Working, acidotic tissue extracts more oxygen. Alkalosis does the opposite.
• Temperature: fever right-shifts; hypothermia left-shifts. A cold, alkalotic, stored unit is a poor unloader until the recipient warms it and restores metabolites.

Stored red cells lose 2,3-DPG, so the curve is left-shifted on the day of issue. The recipient usually regenerates 2,3-DPG over about 12–24 hours. Do not invent a rule that a day-42 unit “does not carry oxygen.” It binds oxygen; it unloads it less readily until 2,3-DPG returns. Rejuvenation (Chapter 4.1) is the manufacturing attempt to wind that metabolite clock backward before wash or freeze.

Cell survival and the storage lesion

Circulating red-cell lifespan is about 120 days. Roughly 1% of red-cell mass turns over each day. A single unit is a temporary increment if bleeding or hemolysis continues, and an aplastic patient becomes transfusion-dependent because production, not survival, failed.

Platelets circulate about 8–10 days. Aspirin permanently acetylates COX-1 in that platelet, so function stays impaired until new platelets replace the cohort. Neutrophils circulate only hours, which is why granulocytes are collected and issued immediately, not stored like red cells.

Mature red cells have no mitochondria. ATP comes from anaerobic glycolysis (Embden–Meyerhof). The pentose-phosphate pathway (G6PD → NADPH) keeps glutathione reduced and hemoglobin in the ferrous state. ATP runs the Na+/K+ pump that prevents colloid swelling. 2,3-DPG is made by the Rapoport–Luebering shunt off glycolysis — the same pathway that runs down in the refrigerator.

The storage lesion is that metabolism failing at 1–6 °C:

• ATP and 2,3-DPG fall
• pH falls as lactate accumulates
• extracellular potassium rises (pump failure plus leakage)
• membrane flexibility decreases and free hemoglobin slowly rises
• the oxygen curve left-shifts

Additive solutions slow the clock; washing removes supernatant potassium but does not restore 2,3-DPG. A hyperkalemic neonate or an extracorporeal circuit may need a fresher or washed unit for the supernatant chemistry, not because old cells “have no hemoglobin.”

Anemia, polycythemia, and when a unit is indicated

Anemia is reduced red-cell mass. Classify by MCV because the class points to mechanism — the blood bank does not issue “microcytic units”:

• Microcytic — iron deficiency, thalassemia, some anemia of chronic disease
• Normocytic — acute blood loss, hemolysis, marrow failure, mixed deficiency
• Macrocytic — B12/folate deficiency, MDS, some drugs

The transfusion trigger is oxygen-carrying capacity and symptoms, not the MCV. A restrictive threshold near 7 g/dL is the usual exam default for a stable adult without acute coronary ischemia; many cardiac patients are considered near 8 g/dL. Symptomatic anemia, active hemorrhage, and evidence of inadequate oxygen delivery can justify transfusion above those numbers. Asymptomatic iron deficiency at 9 g/dL needs iron, not red cells.

Polycythemia is excess red-cell mass — polycythemia vera, or secondary EPO drive from hypoxia, high-affinity hemoglobin, or a tumor. Viscosity rises and oxygen delivery can fall. The blood-bank action is therapeutic phlebotomy (or declining an ineligible allogeneic donor), never transfusion “to correct the hematocrit.”

Hypovolemia versus anemia is the split this outline line exists to test:

• Hypovolemia — low circulating volume (hemorrhage, dehydration, third-spacing). Perfusion and blood pressure fall. Hematocrit may still be normal until dilution occurs.
• Anemia — low red-cell mass. Chronic anemia is often euvolemic. The patient may be pale and tachycardic without hypotension.

Crystalloid or colloid volume expanders restore perfusion when oxygen-carrying capacity is still adequate. Red cells restore oxygen-carrying capacity. Whole blood or a balanced component ratio restores both in massive hemorrhage. Do not issue red cells as first-line volume to a dehydrated patient with hemoglobin 13 g/dL. Do not treat a hemorrhaging trauma patient with saline alone and call that a hemorrhage protocol.

Worked scenario. A 70 kg adult donates 500 mL. That is ~10% of a 5 L volume. Hematocrit barely moves in the donor chair; plasma refills faster than red-cell mass. The same 500 mL intraoperative loss in a patient whose starting hemoglobin is 7.5 g/dL is a different physiology problem — remaining oxygen-carrying capacity is already near a restrictive trigger.

Exam traps. Blood volume is ~70 mL/kg, not 70 mL total. RBC life is 120 days, platelets 8–10 days. Storage lowers 2,3-DPG (left shift); it does not raise it. Anemia is not hypovolemia. A high hematocrit is a phlebotomy problem. Restrictive transfusion is about oxygen delivery, not a license to ignore bleeding.