ICU · first-part-physiology

Blood and Immunology Physiology — Comprehensive

Also known as Haematopoiesis · Haematopoietic stem cell · Innate immunity · Adaptive immunity · Complement system · Coagulation cascade · Haemostasis · Primary haemostasis · Secondary haemostasis · Fibrinolysis · Antithrombin · Protein C pathway · Tissue factor pathway · Natural anticoagulants

Blood and immunology physiology — the integrated biology of haematopoiesis, innate and adaptive immunity, haemostasis (primary + secondary), fibrinolysis, and the natural anticoagulant regulatory systems. HAEMATOPOIESIS: pluripotent haematopoietic stem cell (HSC) in bone marrow → self-renewal + differentiation down two lineages. MYELOID lineage → erythrocytes (EPO-driven), neutrophils (G-CSF), monocytes/macrophages (M-CSF), eosinophils (IL-5), basophils, and megakaryocytes/platelets (TPO). LYMPHOID lineage → T cells (thymus), B cells (marrow), NK cells. Common progenitors: CMP (common myeloid progenitor, driven by IL-3/GM-CSF) and CLP (common lymphoid progenitor). INNATE IMMUNITY (minutes-hours): neutrophils (phagocytosis + neutrophil extracellular traps [NETs]), macrophages (phagocytosis + antigen presentation via MHC II), dendritic cells (professional antigen presenters bridging innate→adaptive), NK cells (kill virus-infected/tumour cells lacking MHC I, regulated by activating/inhibitory receptors), complement (classical [antibody-triggered, C1q], alternative [spontaneous hydrolysis of C3, amplification], lectin [mannose-binding lectin → MASP] pathways → converge at C3 convertase → C5 → membrane attack complex [MAC, C5b-9] → osmotic lysis + opsonisation [C3b] + inflammation [C3a/C5a]), acute phase proteins (CRP, procalcitonin, ferritin — produced by liver under IL-6 drive). ADAPTIVE IMMUNITY (days-weeks): T cells (CD4+ helper — coordinates response via cytokines, Th1/Th2/Th17/Tfh/Treg; CD8+ cytotoxic — kills virus-infected cells via perforin/granzyme + FasL), B cells (plasma cells produce antibody; IgM first then class-switching to IgG/IgA/IgE; memory B cells) → immunological memory. PRIMARY HAEMOSTASIS: platelet adhesion (vWF binds exposed subendothelial collagen + platelet GPIb-IX-V) → activation (shape change, granule release: ADP, serotonin, TXA2 from COX/thromboxane synthase; GPVI signals) → aggregation (GPIIb/IIIa [αIIbβ3] binds fibrinogen → platelet plug). SECONDARY HAEMOSTASIS: EXTRINSIC pathway (tissue factor + VIIa → activates X → tenase), INTRINSIC pathway (XII → XI → IX + VIIIa → activates X — amplification loop), COMMON pathway (X → Va → prothrombinase → thrombin [IIa] → fibrinogen → fibrin → cross-linked by XIIIa). FIBRINOLYSIS: plasminogen → plasmin (via tPA from endothelium; uPA) → degrades fibrin → D-dimer (and FDPs); regulated by PAI-1 (inhibits tPA) and α2-antiplasmin. REGULATION (natural anticoagulants): ANTITHROMBIN (serpin — inhibits thrombin, IXa, Xa, XIa, XIIa — potentiated ~1000-fold by heparin via conformational activation of its reactive site and the heparin-binding lysine); PROTEIN C/S (thrombin-thrombomodulin on endothelium activates protein C → activated protein C [APC] + protein S as cofactor → inactivates Va and VIIIa by proteolysis; deficiency → thrombophilia); TFPI (tissue factor pathway inhibitor — inhibits VIIa-TF complex after Xa generation, feedback inhibition of extrinsic pathway). The endothelial glycocalyx + thrombomodulin + heparan sulfates + tPA + ADAMTS13 maintain a constitutive anti-thrombotic vessel surface.