2.2 Blood Cells, Immunity, Hemostasis, Fibrinolysis & Blood Distribution

Why this area matters

The 2025 Physiology TOS lists "blood cells: characteristics and functions including immunologic, blood clotting and fibrinolytic pathway and blood flow and distribution" inside the general and cellular physiology area. The same physiology later supports Pathology (bleeding disorders, anemia), Pharmacology (anticoagulants) and Medicine (dengue, DIC). Learn it as a set of mechanisms you can apply to a laboratory pattern.

Composition of blood and the red cell

Blood is about 55% plasma and 45% cells; the cell fraction is the hematocrit. Total blood volume is about 70 mL/kg in adults, or 5 L in a 70-kg man.

• Red cells are biconcave discs without nuclei or mitochondria. They make ATP only through glycolysis, and they use the Rapoport-Luebering shunt to produce 2,3-BPG, which lowers hemoglobin's oxygen affinity. They also depend on the pentose phosphate pathway (G6PD) for NADPH against oxidant stress. They circulate for about 120 days and are removed mainly by splenic macrophages.
• Erythropoiesis is driven by erythropoietin, which peritubular interstitial cells of the renal cortex secrete when renal tissue oxygen falls (anemia, altitude, lung disease). Effective production needs iron, vitamin B12 and folate. The reticulocyte count shows whether the marrow is responding: it is high after bleeding or hemolysis and low in marrow failure or nutrient deficiency.
• Normal indices: MCV 80 to 100 fL. Microcytosis points to iron deficiency or thalassemia; macrocytosis points to B12 or folate deficiency.

Leukocytes and the immune functions of blood

Innate immunity (neutrophils, macrophages, complement, NK cells) responds within hours and has no memory. Adaptive immunity (B and T lymphocytes) is specific, takes days on first exposure, and leaves memory cells. That memory is the basis of vaccination.

Hemostasis: the four steps

1. Vascular spasm. Injured vessels constrict, helped by thromboxane A2 and endothelin.
2. Platelet plug (primary hemostasis).
   • Platelets (150,000 to 450,000/µL; lifespan 7 to 10 days; produced by megakaryocytes under thrombopoietin from the liver) adhere when glycoprotein GpIb binds von Willebrand factor on exposed collagen.
   • They activate, releasing ADP and thromboxane A2.
   • They aggregate as fibrinogen bridges GpIIb/IIIa receptors on neighboring platelets.
3. Coagulation (secondary hemostasis). Tissue factor-VIIa starts the extrinsic pathway. Factors XII, XI, IX and VIII form the intrinsic pathway. Both converge on the common pathway (X, V, prothrombin [II] and fibrinogen [I]). Thrombin turns fibrinogen into fibrin, and factor XIIIa cross-links it. Calcium (once called factor IV) and platelet phospholipid are required at several steps.
4. Clot retraction and repair, followed by fibrinolysis.

Vitamin K-dependent proteins: factors II, VII, IX and X, plus proteins C and S. All need gamma-carboxylation, which warfarin blocks.

Natural anticoagulants:

• antithrombin, which inactivates thrombin and Xa and is accelerated about a thousandfold by heparin;
• protein C with protein S, which inactivate Va and VIIIa (factor V Leiden resists this);
• tissue factor pathway inhibitor.

Fibrinolysis

Tissue plasminogen activator (tPA) from endothelium converts plasminogen into plasmin. Plasmin digests fibrin and releases D-dimers. Alpha-2 antiplasmin and plasminogen activator inhibitor-1 (PAI-1) restrain the system. In disseminated intravascular coagulation, clotting and fibrinolysis run at the same time: platelets fall, PT and aPTT lengthen, fibrinogen drops and D-dimer rises.

Reading the screening tests

Blood groups

ABO antigens sit on red cells. Plasma carries naturally occurring IgM antibodies against the antigens a person lacks. Group O red cells can be given to any ABO group; group AB patients can receive red cells of any ABO group. Antibodies to Rh(D) are IgG, which crosses the placenta, so anti-D immunoglobulin is given to Rh-negative mothers to prevent hemolytic disease of the fetus and newborn.

Blood flow and distribution

At rest, about 84% of blood volume is in the systemic circulation: 64% in veins, 13% in arteries and 7% in arterioles and capillaries. The remaining 16% is in the heart (7%) and pulmonary vessels (9%). Veins are therefore the body's blood reservoir, and venoconstriction after hemorrhage mobilizes this volume.

The resting cardiac output of about 5 L/min is shared roughly as follows: splanchnic and liver 27%, kidneys 22%, skeletal muscle 15%, brain 14%, skin 6%, bone 5%, heart 4%. During exercise, muscle flow can rise many-fold while splanchnic and renal flow fall. Blood viscosity rises with hematocrit, so polycythemia increases resistance to flow.