Blood And Is

BLOOD and HEMOSTASIS Delfin Arnel Razon, MD, DPBA Department of Medical Physiology Pamantasan ng Lungsod ng Maynila College of Medicine

Overview of Blood Tissue • Connective tissue with liquid matrix (plasma) • Flows within the cardiovascular system • Volume: = 71ml/kg (5L in a 70 Kgm adult) • 55% is fluid; 45% formed elements • Primary Functions: – Transport of molecules – Exchange between tissues and between internal/external environment

• Secondary functions: – Immunity – Thermoregulation – Fluid volume homeostasis – pH homeostasis

The Red Blood Cells (erythrocytes) • Shape • 5.2 m /cubic milliliter (male); 4.7m (female) • Transport of O2 • Control of blood pH • Life span = ~120 days

hemoglobin molecule

Rh angglutinogen

• D antigen = Rhesus (+); DD, Dd • d antigen = Rhesus (-); dd; • Hemolytic disease of the newborn

Regulation of RBC production

• • • •

>erythropoietin > Cyanocobalamin (vit B12) > folic acid > iron metabolism

The White Blood Cells (Leukocytes)

The White Blood Cells (Leukocytes) • • • • •

Neutrophils 62% Eosinophils 2.3% Basophils 0.4% Monocytes 5.3% Lymphocytes 30% B cells plasma cells T cells cytotoxic T cells helper T cells suppressor T cells NK cells • Platelets 150,000-300,000

PHAGOCYTOSIS

Inflammation

Mediators of Inflammation: • Tumor Necrosis Factor (TNF) • Interleukin-1 (IL-1) • Granulocyte-monocyte colony stimulating factor (GM-CSF) • Granulocyte colony stimulating factor (G-CSF) • Monocyte colony stimulating factor (MCSF)

PRINCIPAL CYTOKINES • IL-1 (à and β) = phagocyte activation, inflammation and fever; hematopoiesis • IL-2 = proliferation of T8 and B cells • IL-3, G-CSF, M-CSF, GM-CSF= hematopoiesis • IL-4 = differentiation of B cells and basophils • IL-5 = b cell activation; eosinophil differentiation • IL-6 = increased synthesis and secretion of Igs by B cells

• IL-7 = proliferation of T and B cells • TNF = fever; hemorrhagic necrosis in tumors; lysis of bone • TNF-beta = sama action as TNF • Alpha INF = antiviral; antiproliferative; induces NK cells • Beta-IFN = antiviral, antiproliferative • Gamma-IFN = activates macrophages • PDGF = mitogen for vascular smooth muscle; fosters wound healing • PAF = platelet aggregation; inflammatory processes inc activation of neutrophils , bronchoconstriction, ↑ capillary permeability

• RESPIRATORY BURST -formation of superoxides/H2O2 • SIGNAL TRANSDUCTION/STIMULUS RESPONSE

HEMOSTASIS

HEMOSTASIS

CLOT FORMATION vs. CLOT BREAKDOWN

• 1. Adhesion - exposure to collagen - binding to vWF via GPIb receptor 2. Accumulation and aggregation - TXA2 synthesis - fibrinogen binding 3. Surface coagulation - platelet membrane phospholipid facilitates coagulation 4. Consolidation - clot contraction via platelet actin-myosin PROCESSES INVOLVED IN THE FORMATION OF PLATELET PLUG

P L

ARACHIDONIC ACID

A T E L

Cyclic endoperoxides

E

V E W A S L S L E L

T S

Thromboxane A2 TXA2

Prostacyclin PGI2

Induces Platelet Aggregation

Inhibits Platelet Aggregation

THROMBIN

FIBRINOGEN

STABLE FIBRIN CLOT

Inhibitors of Blood Coagulation

• • • •

1. Anti thrombin III 2. Heparin co factor II 3. Activated Protein C 4. Tissue Factor Pathway Inhibitor

.E . N . D .