The Circulatory System: Blood Chapter 18

Transcription

1 The Circulatory System: Blood Chapter 18 Functions and properties of blood Plasma Blood cell production Erythrocytes Leukocytes Blood Types Hemostasis

2 Functions and Properties of Blood Functions in respiration, nutrition, waste elimination, thermoregulation, immune defense, water balance, electrolyte and ph balance Adults have 4-6 L of blood composed of: plasma, a clear extracellular fluid formed elements = blood cells and platelets Properties of blood: viscosity = resistance to flow osmolarity = concentration of dissolved particles

3 Hematocrit Centrifuge separates formed elements from plasma Hematocrit is the percent of total volume that is cells Normal hematocrit values Female: 37-48% Male: 45-53%

4 Plasma and Plasma Proteins Plasma is a mixture of proteins, enzymes, nutrients, wastes, hormones, and gases if allowed to clot, the liquid that remains is called serum 3 major categories of plasma proteins: albumins are the most abundant plasma protein contributes to viscosity and osmolarity and influences blood pressure, flow and fluid balance fibrinogen is precursor of fibrin threads that help form blood clots globulins (antibodies) provide immune system defenses alpha, beta and gamma globulins Albumens and fibrinogen plasma proteins are formed by the liver Globulins are antibodies produced by white blood cells called plasma cells

5 Plasma and Serum Blood to which an anticoagulant has been added will not clot. Blood cells will settle to the bottom of the tube leaving plasma at the top of the tube. Blood to which no anticoagulant has been added will clot. Blood cells get caught in the clot leave serum behind.

6 Non-protein Components of Plasma Nitrogenous compounds amino acids from dietary protein or tissue breakdown nitrogenous wastes (urea and ammonia) are toxic end products of catabolism that are normally removed from the blood by the kidneys Nutrients (glucose, vitamins, fats, minerals) Dissolved gases like O 2 and CO 2 are transported in plasma Many electrolytes (Na +, Cl +, K +, HCO 3-, Ca +2, and others) sodium makes up 90% of plasma cations accounting for more of the blood s osmolarity than any other solute

7 Formed Elements of Blood neutrophil eosinophil erythrocyte monocyte lymphocyte platelets basophil Formed Elements = Erythrocytes, Platelets, Leukocytes (neutrophil, eosinophil, basophil, monocyte, lymphocyte) Non-formed Elements = Plasma

8 Blood Cell Production (Hematopoiesis/Hemopoiesis) The following hematopoietic tissues produce blood cells: yolk sac of vertebrate embryos produce stem cells that colonize fetal bone marrow, liver, spleen lymph nodes and thymus liver stops producing blood cells at birth and the thymus stops at about age 10, but the other tissues continue to produce WBCs bone marrow contains stem cells that produce RBCs, WBCs and platelets Stem cells multiply continually and are pluripotent (capable of differentiating into multiple cell lines) Red bone marrow is active; yellow bone marrow is inactive and fatty Stem cells are stimulated by hormones including erythropoietin (EPO) from the kidney and the liver

9 amniotic sac yolk sac placenta

10 Stem Cells of Hematopoiesis

11 Erythrocytes (RBCs) Biconcave Disc-shaped cells 7.5 M diameter, 2.0 m thick at rim Flexible center allows folding so cells can pass through narrow capillaries More surface area than a simple disk facilitates diffusion rate of gasses in and out of the cell Major function of RBCs is gas transport Loses nucleus and most organelles during maturation resulting in increased surface area/volume ratio 33% of cytoplasm is hemoglobin (Hb) O 2 delivery to tissues and CO 2 transport back to lungs contains the enzyme, carbonic anhydrase (CA) that produces carbonic acid from CO 2 and water which plays an important role in gas transport and ph balance RBC count normal values men million RBCs/ L women million RBCs/ L

12 Erythrocytes on the tip of a Needle

13 Flexible center of erythrocytes allows folding so cells can pass through narrow capillaries. Capillaries are formed by cells called Endothelial Cells

14 Erythrocyte Production Erythropoiesis from stem cells in bone marrow produces 2.5 million RBCs/second. In response to erythropoietin (EPO), some stem cells develop into proerythroblasts which multiply and develop into erythroblasts. Erythroblasts multiply, synthesize hemoglobin and develop into normoblasts. Normoblasts synthesize more hemoglobin, discard their nucleus and develop into reticulocytes. Reticulocytes have a reticulated pattern of nuclear debris and a welldeveloped network of endoplasmic reticulum that was used for hemoglobin synthesis. a few reticulocytes enter the bloodstream before they fully mature into erythrocytes and can be 0.5% to 1.5% of the circulating RBCs Development from a stem cell to a RBC takes 3-5 days and involves: reduction in cell size, increase in cell number, synthesis of hemoglobin, loss of nucleus blood loss speeds up the process increasing reticulocyte count in circulating blood which is called a shift to the left

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16 Erythrocyte Homeostasis Negative feedback control kidney and liver hypoxia EPO production bone marrow stimulation RBC count in 3-4 days Causes of Hypoxia low levels of atmospheric O 2 high elevation or altitude increase in exercise Endurance-trained athletes have RBC counts as high as 6.5 million/ l (normal range is 4-6 million) inhaling carbon monoxide hemorrhage

17 Nutritional Needs for Erythropoiesis Iron is key nutrient for erythropoiesis Iron is lost daily through urine, feces, and bleeding on average, men lose 0.9 mg/day and women lose 1.7 mg/day low absorption rate requires consumption of 5-20 mg/day dietary iron comes in 2 forms: ferric (Fe +3 ) and ferrous (Fe +2 ) stomach acid converts Fe +3 to absorbable Fe +2 gastroferritin from stomach binds Fe +2 and transports it to the intestines absorbed into blood & binds to transferrin to travel to bone marrow and liver liver binds surplus iron to apoferritin to create ferritin for storage erythrocytes use iron to make hemoglobin muscle uses iron to make myoglobin which stores O 2 all cells use iron to make cytochromes in mitochondria Other nutritional requirements include B 12, Folic Acid, Vitamin C and Copper (Cu is used as a cofactor for enzymes)

18 Iron Absorption, Transport & Storage

19 Hemoglobin Normal, adult hemoglobin (Hb A ) consists of 4 protein chains called globins (2 alpha chains and 2 beta chains). Each globin has a heme group which binds oxygen to ferrous ion (Fe +2 ). Each Hb molecule can carry four O 2 molecules. Fetal hemoglobin (Hb F ) has gamma instead of beta chains HbF has a higher affinity for O 2 than HbA enabling the fetus to extract O 2 from the mother s bloodstream

20 Erythrocytes and Hemoglobin RBC count and hemoglobin concentration determine the amount of oxygen the blood can carry. Hemoglobin concentration of whole blood: men 13-18g/dL women 12-16g/dL (dl = deciliter = 100ml) Why are values are lower in women? androgens that stimulate RBC production are lower in women women may have periodic menstrual loss of blood

21 Erythrocyte Disorders Polycythemia is an excess of RBCs primary polycythemia is due to cancer of erythropoietic cell line in the red bone marrow RBC count as high as 11 million/ L (normal range is 4-6 million / L) hematocrit of 80% secondary polycythemia can result from dehydration, high altitude, or physical conditioning RBC count of 8 million/ L Dangers of polycythemia increased blood viscosity can lead to embolism, stroke or heart failure

22 Anemia = Deficiency of RBCs or Hb Types of anemia iron-deficiency anemia hemorrhagic anemias from loss of blood hemolytic anemias from RBC destruction Effects of anemia tissue hypoxia and resulting necrosis low blood osmolarity and resulting tissue edema low blood viscosity and resulting increased heart rate

23 Sickle-Cell Disease

24 Sickle-Cell Disease Sickle-Cell is a hereditary defect in Hemoglobin (Hb S ) Recessive allele modifies hemoglobin structure Caused by a single amino acid substitution (valine is inserted in the protein where a glutamic acid should be) homozygous for Hb S have sickle-cell disease heterozygous for Hb S have sickle-cell trait but rarely have symptoms Most common in African Americans and people from Mediterranean region Implications of sickle-cell disease: Hb S turns to gel (polymerizes) at low oxygen concentrations causing cell elongation and inflexible sickle shape that is prone to lysis Sickle cells are sticky and agglutinate, blocking vessels, causing intense pain, kidney and heart failure, paralysis, and stroke chronic hypoxia activates hematopoietic tissue producing more deformed cells Hb S gene persists despite its harmful effects to the homozygous individual because it protects from malaria Hb S indigestible by malaria parasites

25 The ABO Group Your ABO blood type is determined by presence or absence of antigens (agglutinogens) A and/or B on RBCs blood type A has A antigens blood type B has B antigens blood type AB has both A and B antigens blood type O has neither antigen Frequency of blood types varies among populations, but in the USA, O is the most common and AB is the rarest.

26 Frequency of ABO Blood Groups Population O A B AB Cherokee, NC, USA 95% 4% 2% 0% Pawnee, OK, USA 58% 40% 3% 0% African-American, USA 51% 25% 19% 4% Caucasian, USA 46% 42% 9% 4% Eskimo, USA 47% 45% 6% 2% Nikappu, Japan 31% 38% 22% 9% Bengali, India 30% 26% 36% 7%

27 Agglutinins against the ABO Group Antibodies (agglutinins) against the A and B antigens appear 2-8 months after birth and reach a maximum concentration at 10 about years. you do not normally produce antibodies that would react against your own antigens (agglutinogens). each antibody can attach to several antigens at the same time causing agglutination (clumping) of red blood cells.

28 RBC antigens called agglutinogens A & B ABO Blood Types inherited combinations of proteins, glycoproteins and glycolipids on red blood cell membranes Plasma antibodies called agglutinins anti-a & B agglutinins are gamma globulins in blood plasma that recognize (stick to) foreign agglutinogens on RBCs responsible for RBC agglutination in mismatched blood transfusions

29 ABO Blood Types

30 Agglutination of Erythrocytes

31 ABO Blood Typing

32 Mismatched Transfusion Reaction Agglutinated RBCs block blood vessels and RBCs can rupture free Hb can block kidney tubules and cause death Universal donors and recipients AB called universal recipient since it lacks both antibody A and B; O called universal donor problem is donor s plasma may have antibodies against recipient s red blood cells solution is giving packed cells with minimum plasma

33 The Rh Group Rh or D agglutinogens were discovered in the Rhesus monkey in 1940, and then a similar system was found in humans.

34 The Rh Group Blood type is Rh+ if type D agglutinogens are present on RBCs Anti-D agglutinins are not normally present in blood and only form in Rh- individuals who are exposed to Rh+ blood: Rh- person gets a blood transfusion of Rh+ blood Rh- woman carrying an Rh+ fetus no problems result with either the first transfusion or the first pregnancy Hemolytic Disease of the Newborn (HDN or erythroblastosis fetalis) occurs if mother has formed anti-d antibodies and is pregnant with 2nd Rh+ child RhoGAM TM can be given to a pregnant woman with a fetal Rh incompatibility RhoGAM binds to fetal agglutinogens that get into in the mother s blood so her immune system will not mount an attack against the fetus during pregnancy

35 Hemolytic Disease of Newborn In the first pregnancy, some fetal Rh+ blood crosses into the mother and she slowly develops anti-d agglutinins In second pregnancy, the mother s antibodies can cross into the fetus and hemolyze the fetal blood causing severe anemia in the baby. Hemolyzed RBCs release hemoglobin which is converted to bilirubin. High bilirubin is toxic to the mother and child and can cause brain damage. Treat with transfusion or UV phototherapy to degrade bilirubin.

36 There is a dominant allele for the D antigen. The genetic pairs that can exist in humans are as follows: Genetic makeup Blood type + + Rh positive + - Rh positive - - Rh negative Parents' Possible allele Possible Rh Rh types combinations in the children Both & positive Both & or + - positive Both & or + - or - - positive or negative Both & negative One + & One & positive One + & One & or - - positive or negative

37 Frequency of Rh Blood Groups Population + - Cree, Quebec 98% 2% African-American, USA 85% 15% Caucasian, USA 85% 15% Eskimo, USA 100% 0% Bengali, India 95% 5%

38 Leukocytes (WBCs) 4,500-10,000 white blood cells/mcl (cells per microliter) Granulocytes contain specific granules eosinophils - pink-orange granules and bilobed nucleus (2-4%) basophils - abundant, dark violet granules (<1%) large U or S-shaped nucleus hidden by granules neutrophils - multilobed nucleus (60-70%) Very lightly stained reddish to violet granules in cytoplasm Agranulocytes contain no noticeable granules lymphocytes - round, uniform dark violet nucleus (25-33%) variable amounts of bluish cytoplasm (scanty to abundant) monocytes indented nucleus (3-8%) large cell with abundant cytoplasm

39 Granulocytes Neutrophils ( in bacterial infections) phagocytosis of bacteria releases antimicrobial chemicals Eosinophils ( in parasitic infections or allergies) phagocytosis of antigen-antibody complexes, allergens and inflammatory chemicals release enzymes that destroy parasites such as worms Basophils ( in inflammation or infection) secrete histamine (vasodilator) secrete heparin (anticoagulant)

40 Agranulocytes Lymphocytes ( in diverse infections and immune responses) destroy cancer cells, foreign cells, virally infected cells coordinate actions of other immune cells secrete antibodies and provide immune memory two groups: T-lymphocytes and B- lymphocytes Monocytes ( in viral infections and inflammation) mature into macrophages that consume (phagocytosis) pathogens and debris present antigens to activate other immune cells

41 Abnormalities of Leukocyte Count Leukopenia = low WBC count (<5000/ L) causes: radiation, poisons, infectious disease Leukocytosis = high WBC count (>10,000/ L) causes: infection, allergy and disease Leukemia = cancer of hemopoietic tissue myeloid (granulocyte) or lymphoid (lymphocyte) effects: patient subject to opportunistic infection, anemia and impaired clotting

42 Normal and Leukemia Blood Smears

43 Megakaryocytes and Platelets Megakaryocytes are bone marrow cells that repeatedly replicate their DNA without dividing megakaryocytes are gigantic cells (100 m diameter) with a huge nucleus megakaryocytes remain in the bone marrow Megakaryocytes release fragments that enter the bloodstream as platelets platelets live for about 10 days some platelets are stored in the spleen and can be released as needed

44 Megakaryocytes & Platelets

45 Science volume September 2007 p. 1689

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47 Platelets Platelets are small fragments of megakaryocytes platelets are only 2-4 m diameter platelets contain granules used in clot formation platelets have pseudopods used for phagocytosis and clot retraction Normal Count: 130,000 to 400,000 platelets/ L Functions secrete clotting factors, growth factors for endothelial repair, and vasoconstrictors in broken vessels form temporary platelet plugs attract WBCs to sites of inflammation retract and eventually dissolve old blood clots

48 Hemostasis 1) Vascular Spasm: Vasoconstriction reduces bleeding 2) Platelet Plug Formation: platelets adhere to exposed collagen fibers 3) Blood Clotting: RBCs and more platelets become enmeshed in fibrin threads

49 1) Vascular Spasm Prompt constriction of a broken blood vessel Triggers for a vascular spasm: some pain receptors directly innervate smooth muscle surrounding the blood vessel lasts only a few minutes injury to smooth muscle longer-lasting constriction platelets release serotonin which is a chemical vasoconstrictor

50 2) Platelet Plug Formation Normal endothelium is very smooth and is coated with prostacyclin (an ecosanoid that repels platelets) Broken vessel exposes rough surfaces of collagen Platelet plug formation: platelet pseudopods stick to damaged vessel and other platelets pseudopods contract and draw walls of vessel together forming a platelet plug platelets degranulate releasing a variety of substances serotonin is a vasoconstrictor thromboxane, an eicosanoid that promotes aggregation and degranulation of platelets and vessel vasoconstriction Positive feedback cycle is active until break in vessel is sealed

51 3) Blood Clotting (Coagulation) Clotting is the most effective defense against bleeding conversion of soluble plasma protein fibrinogen into insoluble fibrin threads that form the framework of a clot Clotting Factors are always present in the plasma and in tissues activating one factor will activate the next to form a reaction cascade Factors released by damaged blood vessel tissues cause the extrinsic cascade pathway to begin. Factors found only in the blood itself causes the intrinsic cascade pathway to begin (platelet degranulation). Both cascades normally occur together and lead to a fibrin clot.

52 Colorized scanning electron micrograph of a blood clot removed from the coronary artery of a patient with acute myocardial infarction showing he fibrin meshwork (brown) with trapped red blood cells and a cholesterol crystal (yellow). Science Vol 335 February 10, 2012

53 Coagulation Pathways Extrinsic Pathway Factors released by damaged tissues cause the extrinsic cascade pathway to begin which usually lasts about 15 seconds. Intrinsic Pathway Factors released by platelets start the intrinsic cascade pathway which usually lasts about 3-6 minutes. Calcium is required for both pathways.

54 Completion of Coagulation Both the intrinsic and extrinsic pathways lead to production of Factor X. Factor X produces key enzymes for activating Thrombin which converts soluble fibrinogen into an insoluble fibrin polymer. Thrombin also feeds back on the system to amplify its own production.

55 Coagulation Disorders Unwanted coagulations: Thrombosis = abnormal clotting in unbroken vessel most likely to occur in leg veins of inactive people clots can travel from veins to lungs producing a pulmonary embolism death can occur from hypoxia Embolism: abnormal clot traveling in a blood vessel Infarction, or tissue death, may occur if clot blocks blood supply to an organ Myocardial Infarction (MI) Stroke (brain clot or bleed) 650,000 Americans die annually of thromboembolisms

56 Clot Retraction and Dissolution Clot retraction occurs within 30 minutes pseudopods of platelets pull on fibers of fibrin which compacts the clot Platelet-derived growth factor is secreted by platelets and endothelial cells the growth factor is a mitotic stimulant for fibroblasts and smooth muscle that multiply and repair the damaged vessel Fibrinolysis or dissolution of a clot Fibrin is broken down by the enzyme plasmin Plasmin is produced by the intrinsic enzyme kallikrein and the extrinsic enzyme TPA (tissue plasminogen activator)

57 Blood Clot Dissolution Positive Feedback TPA Kallikrein in the plasma and TPA (tissue plasminogen activator) from damaged tissues quickly convert inactive plasminogen into plasmin Plasmin breaks down clots and promotes formation of more kallikrein

58 Dissolving Clots Streptokinase Enzyme made by the Streptococcus bacteria dissolves clots when administered intravenously. Relatively non-specific and digests many proteins. Tissue plasminogen activator (TPA) Specifically converts inactive plasminogen into the clot-dissolving enzyme plasmin Now produced by transgenic bacteria. Hementin Anticoagulant produced by the giant Amazon leech, Haementeria. Used to dissolve clots in cardiac patients. Now produced in transgenic bacteria.

59 Medicinal Leeches Removing Clots from a postsurgical hematoma

60 Prevention of Clots Platelet Repulsion: platelets do not adhere to prostacyclin-coating that normally lines blood vessels Thrombin Dilution: thrombin is normally diluted by circulating blood heart slowing, as during shock, can result in clot formation slow venous return in legs due to prolonged sitting can also result in clot formation Anticoagulants heparin secreted by basophils and mast cells during inflammatory response interferes with formation of clotting factors (prothrombin activator) Drugs like coumadin

61 Hemophilia Genetic lack of clotting factors hemophilia A is missing factor VIII (83% of cases) hemophilia B is missing factor IX (15% of cases) hemophilia C is missing factor XI (rare) Symptoms: physical exertion can cause bleeding and excruciating pain Treatments: transfusion of plasma or purified clotting factors factor VIII is now produced by transgenic bacteria

62 Normal Blood Values Adults have 4-6 L of blood Female Male Hematocrit: 37-48% 45-53% Hemoglobin: 12-16g/dL 13-18g/dL RBC count: million/ L million/ L WBC count: 4,500-10,000/ L neutrophils 60-70% eosinophils 2-4% basophils <1% lymphocytes 25-33% monocytes 3-8% platelet count: 130,000 to 400,000/ L