Blood. Hematology the study of blood

Transcription

1 Blood Hematology the study of blood 1

2 Blood Sticky, opaque fluid with a metallic taste (Fe 2+ ) Color varies from scarlet (oxygenated) to dark red (deoxygenated) ph is between 7.35 and 7.45 Average volume in an adult is 5 L 7% of body weight 2 L = blood cells (formed elements) 3 L = plasma fluid portion of blood (ECF) Functions include: Substance distribution Body protection clot formation (prevents blood loss) immune system activation (prevents infection) 2

3 Components of Blood Centrifugation separates blood based on density Plasma (least dense) ~58% of whole blood volume Formed Elements (cells) Buffy coat layer of platelets and white blood cells (WBCs) less than 1% of whole blood volume Erythrocytes (red blood cells (RBCs)) (most dense) 42% of whole blood volume Hematocrit (Hct) 1 μl = 1/1,000,000 L of blood contains: 5,000,000 RBCs 4,000 11,000 WBCs 150, ,000 platelets 3

4 Withdraw blood Centrifuge Plasma (55% of whole blood) Buffy coat: leukocytes and platelets (<1% of whole blood) Erythrocytes (45% of whole blood) Formed elements 18-4

5 Plasma Proteins The presence of proteins makes the osmotic pressure of blood higher than the interstitial fluid which tends to pull water from the interstitial fluid into capillaries Albumins (60% of plasma proteins) carriers for various substances (cholesterol) major contributor to osmotic pressure of plasma Globulins clotting factors, enzymes, antibodies, carriers for various substances (steroid hormones) Fibrinogen forms insoluble protein fibers essential for blood clotting Transferrin iron transport 5

6 Erythrocytes (RBCs) Biconcave disc shape with a diameter of 7.5 mm, Very flexible folds in order to move through some blood vessels that have a diameter smaller (5.0 mm) than the RBC Membranous bags filled with enzymes and Hb no mitochondria (anaerobic fermentation only) no nucleus or endoplasmic reticulum no protein synthesis to make new enzymes, Hb or membrane components leads to increased loss of membrane flexibility making older cells more fragile and prone to rupture life span of an erythrocyte in circulation is ~120 days whereby they are removed by macrophages of the spleen and liver 6

7 Normal Blood Cells 7

8 Blood Cell Formation (Hemopoiesis) The formation of the formed elements is accomplished by the processes of mitosis and differentiation of stem cells called hemocytoblasts in red bone marrow of the humerus and femur, flat bones and coxa The pathway of differentiation of hemocytoblasts depends on the levels of circulating hormones or growth factors that guide the cell down a particular line of development Creation of new erythrocytes: erythropoiesis Creation of new leukocytes: leukopoiesis 8

9 9

10 Erythropoiesis The number of new RBCs entering circulation equals the number of old RBCs removed from circulation (approximately 2,500,000 per second) An increase erythropoiesis is required during times of low oxygen content in blood (hypoxemia) due to: decreased RBCs (anemia) decreased oxygen availability (at high altitudes) increased tissue demand for oxygen (exercising) The liver and kidneys secrete the hormone erythropoietin (epo) in response to hypoxemia erythropoietin stimulates the differentiation of hemocytoblasts into erythrocytes increases RBCs increases the oxygen carrying ability of the blood 10

11 Production of too many red blood cells is a condition called polycythemia which causes an increase blood viscosity (thickness) puts strain on the heart Caused by: over secretion of epo accelerated differentiation of hemocytoblasts severe dehydration which decreases plasma volume 11

12 Polycythemia Polycythemia an excess of RBCs Primary polycythemia (polycythemia vera) Cancer of erythropoietic cell line in red bone marrow RBC count as high as 11 million RBCs/mL; hematocrit 80% Secondary polycythemia From dehydration, emphysema, high altitude, or physical conditioning RBC count up to 8 million RBCs/mL Dangers of polycythemia Increased blood volume, pressure, viscosity Can lead to embolism, stroke, or heart failure 12

13 Anemia Low Hb content in the body caused by: Hemolysis (RBCs rupture at abnormally high rate) Parasitic infections (malaria) hydrolyzes Hb and cytoskeletal proteins that maintain biconcave disc shape becoming more spherical and less deformable Abnormal hemoglobin (sickle cell disease) glutamate valine substitution at 6 th amino acid in β-chain of Hb creating HbS HbS molecules crystallize after unloading O 2 and deforms the RBC into a rigid sickle shape sickled cells tangle with each other as they pass through capillaries causing blood flow blockages sickled cells are removed earlier than normal from circulation (10 20 days) by the spleen due to their deformed/rigid 13 structure

14 Sickle-Cell Disease Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Meckes/Ottawa/Photo Researchers, Inc. 7 µm 14

15 Anemia Low Hb content in the body caused by: Decreased RBC production Iron deficiency anemia lack of iron prevents Hb synthesis results in either low Hct or low Hb Microcytic, hypochromic RBCs Vitamin B 12 deficiency required for RBC synthesis may be due to lack of intrinsic factor secretion from gastric parietal cells Characterized by very large, immature, nucleated erythrocytes Carry less hemoglobin Shorter life span 15

16 Leukocytes (WBCs) Primary cells for the immune system Functions to protect the body from foreign antigens (substances that trigger an immune response) pathogen disease producing biological agent allergen substance that is recognized by the immune system and causes an allergic reaction Leukocytes protect the body via: direct destruction of foreign substances or through the secretion of substances that prevent the spread of these foreign substances 16

17 Leukocytes (WBCs) Capable of leaving the capillaries and functioning extravascularly where they live within tissues for a few hours to several months Leukocytes found in blood in the following proportions: 60% Neutrophils Never 30% Lymphocytes Let 8% Monocytes My 2% Eosinophils Engine 0.4% Basophils Blow Grouped morphologically or functionally 17

18 Functional Groups of Leukocytes Phagocytes engulf and ingest by phagocytosis neutrophils, eosinophils and monocytes (precursor to tissue macrophages) Cytotoxic cells kill cells eosinophils and some T lymphocytes Antigen Presenting Cells (APCs) display foreign proteins (antigens) on their cell surface monocytes and some B lymphocytes 18

19 Morphological Groups of Leukocytes Granulocytes neutrophils, eosinophils, and basophils have multi-lobed nuclei contain visible cytoplasmic granules (vesicles) which are exocytosed to protect against foreign substances Agranulocytes lack visible cytoplasmic granules have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei 19

20 Granulocytes Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neutrophils 10 µm Eosinophil 10 µm Basophil 10 µm all: Ed Reschke 20

21 Agranulocytes Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lymphocyte 10 µm Monocyte 10 µm both: Michael Ross/Photo Researchers, Inc. 21

22 Granulocytes Neutrophils increased numbers in bacterial infections Phagocytosis of bacteria Release antimicrobial chemicals Eosinophils increased numbers in parasitic infections, collagen diseases, allergies, diseases of spleen and CNS Phagocytosis of antigen antibody complexes, allergens, and inflammatory chemicals Release enzymes to destroy large parasites Basophils increased numbers in chickenpox, sinusitis, diabetes Secrete histamine (vasodilator): speeds flow of blood to an injured area Secrete heparin (anticoagulant): promotes the mobility of other WBCs in the area 22

23 Agranulocytes Lymphocytes increased numbers in diverse infections and immune responses Destroy cells (cancer, foreign, and virally infected cells) Present antigens to activate other immune cells Coordinate actions of other immune cells Secrete antibodies and provide immune memory Monocytes increased numbers in viral infections and inflammation Leave bloodstream and transform into macrophages Phagocytize pathogens and debris Present antigens to activate other immune cells antigen-presenting cells (APCs) 23

24 B Lymphocytes B lymphocytes develop in bone marrow insert antibody molecules (proteins that bind to foreign antigens) in their cell membranes which act as surface receptors B cells activated by foreign antigens differentiate into plasma cells which secrete antibodies into blood which bind to and immobilize foreign invaders Antibodies (immunoglobulins) are Y-shaped protein molecules which recognize and bind to antigens When an antibody (work against foreign bodies) binds to an antigen it causes agglutination clumping of cells, held together by antibodies cells are then typically destroyed by the cells of the immune system 24

25 25

26 T Lymphocytes T lymphocytes develop in thymus gland target cells that are infected with viruses, bacteria or parasites by binding to fragments of the antigen that have been digested within a cell and presented on its surface kill infected host cell by releasing perforin and granzymes (related to trypsin and chymotrypsin) perforin creates channels in host cell membrane granzymes enter cell through perforin channels and cause apoptosis 26

27 Platelets Functions Secrete vasoconstrictors that help reduce blood loss Stick together to form platelet plugs to seal small breaks Secrete procoagulants or clotting factors to promote clotting Initiate formation of clot-dissolving enzyme Chemically attract neutrophils and monocytes to sites of inflammation Phagocytize and destroy bacteria Secrete growth factors that stimulate mitosis to repair blood vessels 27

28 Platelets Cell fragments of a megakaryocyte in bone marrow contain many granules filled with clotting proteins and cytokines activated following blood vessel damage release clotting proteins and cytokines to participate in blood clotting (hemostasis) 28

29 Hemostasis Stops bleeding in a 3 step process involving: Platelets Erythrocytes Plasma clotting factors (procoagulants) inactive plasma enzymes that become active in response to a damaged blood vessel aid in the formation of a blood clot 29

30 30

31 Hemostasis 1. Vascular spasms vasoconstriction is caused by vasoconstrictive paracrines released by the endothelium of a damaged blood vessel temporarily decreases blood pressure in damaged blood vessel limiting blood loss 2. Platelet plug formation platelets in the vicinity of the injured blood vessel become activated which causes them to stick to the collagen and one another and secrete cytokines that activates more platelets to aggregate to form a loose plug intact vessel endothelium secretes nitric oxide and prostacyclins to prevent platelet adhesion 31

32 32

33 Hemostasis Coagulation Series of enzymatic reactions that ends in the formation of fibrin (protein fiber mesh that stabalizes the platelet plug) Divided into 2 pathways that merge into 1: 1. Intrinsic pathway begins with the exposure of clotting factor XII to collagen which activates factor XII 2. Extrinsic pathway begins when damaged tissues release tissue factor (clotting factor III) into the blood which activates clotting factor VII The intrinsic and extrinsic pathways unite at the common pathway to create thrombin Thrombin converts the soluble plasma protein fibrinogen into the insoluble protein fibrin Thrombin activates factor XIII which converts fibrin into a crosslinked polymer that stabilizes the clot 33

34 Anticoagulants are compounds that interfere with coagulation 34

35 35

36 Blood Types Antigens Cell surface molecules that are unique to the individual Antibodies Used to distinguish self from foreign matter Foreign antigens generate an immune response Agglutinogens antigens on the surface of the RBC that is the basis for blood typing Proteins (gamma globulins) secreted by plasma cells Agglutination Part of immune response to foreign matter Bind to antigens and mark them for destruction Forms antigen antibody complexes Agglutinins antibodies in the plasma bring about transfusion mismatch Antibody molecule binding to antigens Causes clumping of red blood cells 36

37 ABO Blood Groups Human blood types are determined by the presence or absence of 2 types of antigenic glycoproteins in the membrane of RBCs 1. ABO blood group antigens A antigen B antigen 2. Rh antigen Someone with the Rh antigen on the RBCs is positive Someone without the Rh antigen on the RBCs is negative 37

38 38

39 ABO Blood Groups Problems with transfusions arise because plasma normally contains antibodies to the ABO antigens People make antibodies to the RBC antigens that they do NOT possess Type A has anti-b antibodies Type B has anti-a antibodies Type AB has no antibodies in the plasma Type O has both anti-a and anti-b antibodies Rh positive blood does NOT have anti-rh antibodies in their plasma Rh negative blood has anti-rh antibodies in their plasma 39

40 ABO Blood Typing Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Type A Type B Type AB Type O Claude Revey/Phototake Universal donor Type O: most common blood type Lacks RBC antigens Donor s plasma may have both antibodies against recipient s RBCs (anti-a and anti-b) May give packed cells (minimal plasma) Universal recipient Type AB: rarest blood type Lacks plasma antibodies; no anti-a or anti-b 40

41 Transfusion Compatibilities To determine if a transfusion is compatible, compare the antigens of the donor with the antibodies of the recipient. If they match, then the transfusion will harm the recipient. Blood Type receive from donate to A A, O A, AB B B, O B, AB AB A, B, AB, O universal recipient AB O O A, B, AB, O universal donor Rh + Rh -, Rh + Rh + Rh - Rh - Rh -, Rh + 41

42 42

43 The Rh Group Rh antigens discovered in rhesus monkey in 1940 If antigen is present, a patient is considered blood type Rh + Anti-Rh antibodies are not normally present, but form in Rh - individuals exposed to Rh + blood Rh - woman with an Rh + fetus or transfusion of Rh + blood No problems with first transfusion or pregnancy Occurs if Rh - mother has formed antibodies and is pregnant with second Rh + child Anti-Rh antibodies can cross placenta Prevention RhoGAM given to pregnant Rh - women Binds fetal antigens in her blood so she will not form anti-rh antibodies 43

44 Hemolytic Disease of the Newborn Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. leaves Rh - mother Rh antigen Rh + fetus Second Rh + fetus Uterus Amniotic sac and chorion Anti-D antibody Placenta (a) First pregnancy (b) Between pregnancies (c) Second pregnancy Rh antibodies attack fetal blood causing severe anemia and toxic brain syndrome 44