L11: Blood

Functions of bl:

1. Transport: O2+Hb(RBCs) v.little in plasma, CO2-> RBCs+plasma, nutrient: glu&lipids, -waste products (urea&bilirubin)
2. Regulation: HORMONES (site prod->target tissue), T regulatio-DIVERSION: bl. deeper-superficial vessels
3. Protection: Role of LEUKOCYTES-> INFECTION, CLOTTING

Components of Bl.:

Plasma: H2O, ions, proteins, nutr., horm. wastes

7%pl.w: PROTEINS:

albumins (liver synthesis), globulins (buffers, transport lipids, hormones, vit. metals, clotting enzymes, antibodies), fibrinogens (clot formation, forms bridges between activated pl.)

ELECTROLYTES (Na, K, Ca, Mg,Cl, HCO3, HPO4, SO4):

keep H2O extracellular comp., buffers, bl.clotting role, membrane Xcitability

Leukocytes:WBCs+A/B dye (Leishmans satin): 4000-11000/mm3

Leukopenia >4000/mm3, Leukocytosis<20000/mm3

according to granules:

• GRANULOCYTES (70%): granular : dye blue

neutrophils/polymorphocytes: ↑count->INFECTION, 2-5lobes, IF <3%:>

contain enzymes->breakdown egulfed bac.-> cytoplasm, amaeboid movement, phagocytosis, inflammatory mediators

eosinophils:2lobes, (3lobed), spherical granules, larger than neutro, phagocytic action, Inflammation-ASTHMA

Basophils: granules: HIS, HEPARIN, degranulation: ALLERGIC REACTIONS (skin rash, anaphylactic shock, urticara)

• AGRANULOCYTES: monocytes (2-8%), lymphocytes:large/small (20-40%)

Lymphocytes: Large nucleus, small #granules, lysosomal enzymes

• B-cells: antibody production
• T-cells: Regulation of antibody production
• NK (natural killer) cells: immune responce: lyse target cells

Monocytes: LARGEST OF Bl. cells, irregular, often lobed nucleus, phagocytic-SICKLE CELL ANEAMIA, egulf bac+MALARIA parasites, migrate tissues->differentiate->macrophages

Hematocrit: %RBCs/Bl.V pH: 7.35-7.45, 280-295mOSM

Erythrocytes 120 days life span: Erythropoiesis: regulated (hormone): Eryhtropoietin, O2 delivery-> kidneys, ↓O2-> EPO production-> altitude, lung disease, insuffisient heart pumping, anemia

transport of gases: O2-Hb, CO2

ANEMIA: ↓ ability of O2 transport-> ↓RBCs, ↓[Hg]/RBC

dietary iron deficiency, bone marrow failure: cancer/toxicity, poor EPO production from kidneys, ↑destruction RBCs, SICKLE CELL ANEMIA (Genetic mutation-HbS instead of HbA, Heterocyte≠Malaria, Abnormal Hb forms fibres @ ↓O2, RBS shapes distorted, Capillaries blockage, pain, ↓RBCs lifespan)

Platelets/Thrombocytes: no nucleus, discoid

from Megakaryocytes(multinucleus-> bone marrow)

When ↓pl. # ->↑TPO-> release Thrombopoietin (hormone) from Liver -->> pl. production

ROLE IN DISEASE:

↓pl.count (thrombocytopenia), pl.adhesion/aggregation (Scotts),pl.metabolism

Bl.clotting:

Hematoma: acumulatn of bl. in tissues

Hemostasis: prevent bl.loss in ↓P/small vessels, difficult staunch bl.loss from arteries

THESE CAUSE:

1)PLATELET AGGREGATION (Adherence of platelets to each other)

• Adhension to surface: vessel injury->conformationally changed collagen+
• Pl., Pl.activation: adenosine&serotonin (e-dense granules), adhesive proteins (a-granules): (+) feedback more pl.

(ACTIVATION from collagen (subendothelium), mol. (serotonin) made by themselves)

on activtn: pl. active sites exposed: fibrigonen can bind

• Pl.aggregation
• PLATELET PLUG

2)BL.COAGULATION=CLOTTING/Thrombus around plPLUG: Transformation of bl->solid gel

2Clotting Pathways:

Intrinsic:Begins in bl when exposed to collagen (from traumat. vessels)

Extrinsic: Trauma->vascular membr.: phospholipids+lipoprotein comples

Both lead to formation of :

F13 (XIII)

Prothrombin-> thrombin-> XIIIa

Fibrinogen ->Fibrin monomers -> Stabilised Fibrin

In an UNINJURED vessel: thrombin bound to thrombomodulin activates PROTEIN C: blocks clotting response

Limiting CLOT FORMATION: Plasminogen activators

Plasminogen------Fibrin------->> plasmin

Soluble Fibrin Fragments formed

Liver: critical role: producing&modifying bl.borne proteins (clotting pathways)

bile salts from liver facilitate absorption lipids: diets, VIT.K REQUIRED fro PROTHrombin Synthesis

BLEEDING DISORDERS: CL.factors: liver, Deppresion of Cl.system, NO VIT.K, HEMOPHILIA (male)- abnormality in XIII

HAEMOPOIESIS:bl. cells not replicate, constnt formation: stem cells->foetal liver->bone marrow

Leukopoiesis: (only LYMPHOCYTES): lympoid tissue: lymph, nodes,spleen e.tc.

Erythropoiesis: (+other bl.cells): myeloid tissue: red bone marrow, bones, ribs e.t.c.

PRODUCTION OF BLOOD CELLS: bone marrow (w~liver)- >thrombopoietin, erythropoietin

pluripotent stem cells-> precursors of any bl.cells: 1st differentiation: Lympoid + Myeloi stem cells

HAEMOPOIETIC GROWTH FACTORS: CYTOKINES: regulate production of bl.c. from st.cells, also Thrombopoietin (pl.prod.) from megakaryocytes, reagulate proliferation&differentiation, prevent normal programmed cell death (apoptosis)