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Blood Chapter 17 Blood Composition • Formed Elements = cells (~45%) – Red Blood Cells (RBCs, Erythrocytes) – White Blood Cells (WBCs, Leukocytes) – Platelets • Plasma = soluble materials (~55%) Blood Composition • Percentage of blood that is formed elements – hematocrit – Normal Values Male 42-52% Female 37-47% • Note: WBCs take up <1%, Plasma is majority (55%) ..Blood Composition • Total Blood Volume Male = 5-6 L Female = 4-5 L Plasma • Straw-coloured fluid – ~91-93% water, 7% proteins, 1.5 % other solutes • Nutrients – fats, carbohydrates (glucose), amino acids, minerals, vitamins • Wastes – by-products of living tissue metabolism (creatinine, lactic acid, ammonia, CO2, etc.) Plasma • Plasma Proteins – Albumin (54%) - osmosis and carriers – Globulins (38%)- antibodies – Fibrinogen (7%)- clotting • Other: – oxygen – Electrolytes (Na, K, Ca, Cl, HCO3) – hormones Plasma Proteins • Functions: – Osmotic • albumins pull water back into capillary by osmotic pressure – Antibodies • globulins act to recognize foreign material – Buffers • limit pH changes by taking up H+ • normal pH of blood: 7.35-7.45 (slightly alkaline) – Lipid Transport • Lipoproteins are complexes of fat and protein • eg. LDL’s and HDL’s (High/Low Density Lipoproteins RBCs • Biconcave discs, anucleate, essentially no organelles • Sickle cell – see next slide • 5 million cells/mm3 • Normal Values Male 4.5-6.5 x 1012 /L Female 4.2-5.5 x 1012 /L • Why do men have more? • Does this match with hematocrit values? • Sickle Cell Anemia Inherited condition – predominantly African gene pool – cells lose the biconcave shape when in low oxygen (exercise may deplete O2) – becomes sickle shaped – get lodged in capillaries (often in lungs) – painful and infections can start – Survived genetic selection in Africa because SCA patients don’t tend to suffer as badly from malaria RBCs • ~ 10,000 new cells are made every second to replace 10,000 cells that have died in that second • Where do they get produced? – red bone marrow • Where are they destroyed? – the spleen – recovers iron in heme, uses globin to make amino acids – recycling at its finest RBCs • Cells have no nuclei • packed full of hemoglobin – almost 1/3 of the volume • Normal Values Male 16 2 g/100 mL Female 14 2 g/100 mL • note: g/100 mL is sometimes said “gram percent” RBCs • All that hemoglobin (abbrev. Hb) is meant to carry oxygen • Hypoxia – tissue is starved of O2 – – if Hb does not have enough oxygen, then hypoxia – lips and other tissues may appear blue = cyanotic • When Hb combines with 4 molecules of O2, it’s called Oxyhemoglobin – Loads in lungs – most oxygen in blood is carried this way with some in plasma – most carbon dioxide is carried dissolved in plasma with some in Hb. • What is Deoxyhemoglobin? Where is it formed? • What is Carbaminohemoglobin? Where is it formed? WBCs • Formally called Leukocytes – nucleated – 8,000/mm3 (4 to 10 x 109 /L) • (yes, that’s 4 to 10 billion per litre) – if values fall below this – leukopenia (low WBC count) – if values are above this – leukocytosis (high WBC count) – Why would either occur? WBCs • To Major Groups of Leukocytes – Granular • granules clearly appear within the cytoplasm • form ~70% of all leukoctyes – Agranular – no such granules • Wright’s stain – two dyes produce a neutral stain – Eosin (red) – acidic dye – Methylene blue – basic dye 1. Granular WBCs Neutrophils – 60% of total (most common) – pale lilac in stain (granules take up both red and blue dyes – neutral) – nucleus often multi-lobed • • Phagocytic – bacteria slayers ameboid movement in tissues – • get in tissues by diapedesis = “leaping across” – move across capillary membranes into tissues accumulate as pus around wounds Granular WBCs Eosinophils – 3% of total 2. – – – deep red nucleus and lighter red granules attract red dye (eosin) nucleus looks like phone receiver (bilobed) Increase in response to • • parasitic worms – tapeworms, flukes, pinworms, hookworms) allergies – may lessen response Granular WBCs Basophils – 1% of total (rarest of all) 3. – – – granules stain purplish-black – the basic (methylene blue) dyes nucleus U or S shaped, with obvious constrictions granules contain the Chemicals • • • Histamine – inflammatory response, promotes leaky capillaries (edema), dilates blood vessels and attracts neutrophils Heparin – anticoagulant Function is very similar to Mast cells, though unrelated Agranular WBCs Monocytes – 3-8% of total 1. – – – largest of all leukocytes (several times an RBC) nucleus U or kidney shaped, with obvious constrictions become macrophages • • – migrate to alveoli in lung, connective tissue beneath skin, liver (fixed in place – called Kupffer cells), lymph nodes destroy bacteria cells and viruses by phagocytosis – even some cancer cells did you know…. • a Kupffer cell can destroy a bacterium in < 1/100 seconds? Agranular WBCs Lymphocytes – 25-33% of total (2nd most common) 2. – – – nucleus stains dark-purple, fills most of cell most often found in lymph nodes, spleen important in immune response to disease • T cells – – • B cells – – – mature in bone marrow produce antibodies to recognize foreign material Lymphoblasts • • mature in the Thymus gland act against virus-infected cells and tumour cells produce new lymphocytes and monocytes so, did you notice the three platelets? Platelets • Thrombocytes (Platelets) – megakaryocyte fragments = platelets “large nucleus cells” cell fragments – (not really cells at all) – only ¼ size of lymphocytes – only 400,00/mm3 (140-440 x 109/L) – Note: serum is plasma without platelets won’t clot • Hemostasis Hemostasis = “blood halting” – the formation of a blood clot – loss of blood is stopped when vessels rupture – usually takes only 3-6 minutes – Overview: 3 stages • vascular spasm – dramatic vasoconstriction slow blood flow reduce losses • platelet plug formation - platelets ‘stick’ (adhere) to the wound (collagen fibres) and each other, creating a plug – platelets enhance vascular spasm - serotonin – platelets attract other platelets - ADP • coagulation – cascade of reactions blood transforms into a gel – results are due to a fibrinogen mesh that traps blood cells and seals the hole Hemostasis • Platelets don’t stick to normal (undamaged) endothelium (lining of b.v.’s) or to each other – why? – negative charge of healthy tissue repels them (platelets are also negatively charged) – Damaged tissue loses its negative charge platelets adhere to wounds in b.v. (exposed collagen fibres) – the Platelet Plug is formed, reducing loss of blood – Plasmin Hemostasis • as the wound heals, clot is dissolved • plasmin does this – starts within 2 days of clot formation • dissolves fibrin of clot – Purpura • small reddish or purple spots on skin - petechiae • sub-q bleeding from small vessels • results from insufficient platelet count (thrombocytopenia) – Serotonin • released by platelets • enhances vasoconstriction reduces blood loss Clotting • Two pathways of clot formation – Intrinsic – “found within” • Blood can clot on it’s own in a tube with no external stimulus – Extrinsic – “found without” • Blood clots in response to stimuli from outside eg. chemicals released from damaged cells/tissues • shorter (quicker) path bypasses many steps of intrinsic path – Notes: • There are over 30 substances involved • Many (the “Factors”) are numbered I to XIII » the numbering is NOT in the sequence in which the reaction proceeds • Calcium is ABSOLUTELY essential for clot formation • the main difference between extrinsic and intrinsic pathways is: – extrinsic is a shorter path because of the use of Tissue thromboplastin • all other steps past that stage are shared in common Clotting • Extrinsic Pathway to a Clot – fastest of the two pathways (shortcut) – Tissue Thromboplastin “thrombo” = clot “plastic” = to form • aka Tissue Factor (TF) - produced by damaged cells • becomes Factor X (needs Ca2+) – Factor X • which becomes Prothrombin activator (needs Ca2+) – Prothrombin activator • converts Prothrombin (plasma protein) into Thrombin (enzyme) (needs Ca2+) • Clotting Extrinsic Pathway to a Clot (cont’d.) – Thrombin causes fibrinogen (plasma protein - soluble) to polymerize (join together) into long fibrin strands (insoluble) – Thrombin also activates factor XIII • factor XIII + Ca2+ causes fibrin strands to cross-link forming a web or mesh – Fibrin mesh traps formed elements (platelets, blood cells and fibres) in blood • creates a clot that seals the wound over 3-6 minutes after injury Clotting Extrinsic Clotting • Intrinsic Pathway to a Clot • longer pathway – provoked by • • • • plaques that become rough lining damaged by inflammation rupture of minor vessels platelets adhere to collagen fibres exposed and to themselves – Hageman Factor (Factor XII) • becomes activated by collagen fibres (needs Ca2+) • a cascade through four (4) Factors (needs Ca2+) to become – Factor X • which becomes Prothrombin activator (needs Ca2+) – The rest is the same as for the extrinsic pathway … Intrinsic Helpers along the way • Vitamin K – used indirectly – required by liver to make many of the clotting Factors • Plasma proteins – fibrinogen is converted to fibrin – prothrombin is converted to thrombin – plasmin will dissolve clots • Anticoagulant – prevents clotting eg. heparin (from basophils and mast cells) More on Clottin • Thrombosis – formation of a clot – causes include 1. 2. 3. 4. • injury to b.v. congestion (slow blood flow) polycythemia (viscous blood due to RBC’s hypercoagulability – smoking or high fat diet promotes platelet adherence Embolis – a mobile clot What can you do? • To hasten the formation of a clot a) b) c) d) e) apply gauze (surface for platelets to adhere) apply heat sutures apply fibrin apply thrombin