Blood, a more in-depth examination

1. Blood, a more in-depth examination

2. Section 1: Blood Functions of blood Transportation of dissolved gases, nutrients, hormones, and metabolic wastes Regulation of the pH and ion composition of interstitial fluids Restriction of fluid loss at injury sites Defense against toxins and pathogens Stabilization of body temperature

3. Module 17.1: Blood components Blood Is a fluid connective tissue About 5 liters (5.3 quarts) in body 5–6 in males, 4–5 in females (difference mainly body size) Consists of: Plasma (liquid matrix) Formed elements (cells and cell fragments) Properties Temp is roughly 38°C (100.4°F) Is 5× more viscous than water (due to solid components) Is slightly alkaline (average pH 7.4)

4. Module 17.1: Blood components Whole blood Term for removed blood when composition is unaltered May be fractionated or separated Plasma 46%–63% of blood volume Hematocrit (or packed cell volume [PCV]) Percentage of whole blood contributed by formed elements (99% of which are red blood cells) Average 47% for male (range 40%–54%) Average 42% for female (range 37%–47%)

5. Module 17.1: Blood components Plasma Composition resembles interstitial fluid in many ways Exists because exchange of water, ions, and small solutes 92% water 7% plasma proteins 1% other solutes Primary differences Levels of respiratory gases (oxygen and carbon dioxide) Concentrations of dissolved proteins (cannot cross capillary walls)

6. Module 17.1: Blood components Plasma proteins In solution rather than as fibers like other connective tissues Each 100 mL has ~7.6 g of protein ~5× that of interstitial fluid Large size and globular shapes prevent leaving bloodstream Liver synthesizes >90% of all plasma proteins

7. Module 17.1: Blood components Plasma proteins (continued) Albumins ~60% of all plasma proteins Major contributors to plasma osmotic pressure Globulins ~35% of all plasma proteins Antibodies (immunoglobulins) that attack pathogens Transport globulins that bind ions, hormones, compounds Fibrinogen Functions in clotting and activate to form fibrin strands Many active and inactive enzymes and hormones

8. Module 17.1: Blood components Plasma solutes Electrolytes Essential for vital cellular activities Major ions are Na+, K+, Ca2+, Mg2+, Cl–, HCO3–, HPO4–, SO42– Organic nutrients Used for cell ATP production, growth, and maintenance Includes lipids, carbohydrates, and amino acids Organic wastes Carried to sites of breakdown or excretion Examples: urea, uric acid, creatinine, bilirubin, NH4+

9. Figure 17.1 1 Plasma (46–63%) Whole blood consists of Formed elements (37–54%)

10. Module 17.1: Blood components Formed elements Platelets Small membrane-bound cell fragments involved in clotting White blood cells (WBCs) Also known as leukocytes (leukos, white + -cyte, cell) Participate in body’s defense mechanisms Five classes, each with different functions Red blood cells (RBCs) Also known as erythrocytes (erythros, red + -cyte, cell) Essential for oxygen transport in blood

11. Module 17.1 Review a. Define hematocrit. b. Identify the two components constituting whole blood, and list the composition of each. c. Which specific plasma proteins would you expect to be elevated during an infection?

12. Module 17.2: Red blood cells RBCs in blood Most numerous cell type in blood Roughly 1/3 of all cells in the body Red blood cell count (standard blood test) results Adult males: 4.5–6.3 million RBCs/1 µL or 1 mm3 of whole blood Adult females: 4.2–5.5 million RBCs/1 µL or 1 mm3 of whole blood One drop = 260 million RBCs

13. Module 17.2: Red blood cells RBC characteristics Biconcave disc Average diameter ~8 µm Large surface area-to-volume ratio Greater exchange rate of oxygen Can form stacks (rouleaux) Facilitate smooth transport through small vessels Are flexible Allow movement through capillaries with diameters smaller than RBC (as narrow as 4 µm)

14. Figure 17.2 1 LM x 450 Stained blood smear

15. Figure 17.2 2 The size and biconcave shape of an RBC 7.2–8.4 μm 2.31–2.85 μm 0.45–1.16 μm RBCs Colorized SEM x 1800

16. Figure 17.2 3 The advantages of the biconcave shape of RBCs Functional Aspects of Red Blood Cells • Large surface area-to-volume ration. Each RBC carries oxygen bound to intracellular proteins, and that oxygen must be absorbed or released quickly as the RBC passes through the capillaries. The greater the surface area per unit volume, the faster the exchange between the RBC’s interior and the surrounding plasma. The total surface area of all the RBCs in the blood of a typical adult is about 3800 square meters, roughly 2000 times the total surface area of the body. Rouleaux (stacks of RBCs) Blood vessels (viewed in longitudinal section) • RBCs can form stacks. Like dinner plates, RBCs can form stacks that ease the flow through narrow blood vessels. An entire stack can pass along a blood vessel only slightly larger than the diameter of a single RBC, whereas individual cells would bump the walls, bang together, and form logjams that could restrict or prevent blood flow. Nucleus of endothelial cell Red blood cell (RBC) • Flexibility. Red blood cells are very flexible and can bend and flex when entering small capillaries and branches. By changing shape, individual RBCs can squeeze through capillaries as narrow as 4 μm. LM x 1430 Sectional view of capillaries

17. Module 17.2: Red blood cells RBC characteristics (continued) Lose most organelles including nucleus during development Cannot repair themselves and die in ~120 days Contain many molecules (hemoglobin) associated with primary function of carrying oxygen Each cell contains ~280 million hemoglobin (Hb) molecules Normal whole blood content (grams per deciliter) 14–18 dL (males), 12–16 dL (females) ~98.5% of blood oxygen attached to Hb in RBCs Rest of oxygen dissolved in plasma

18. Module 17.2: Red blood cells Hemoglobin Protein with complex quaternary structure Each molecule has 4 chains (globular protein subunits) 2 alpha (α) chains 2 beta (β) chains Each chain contains a single heme pigment molecule Each heme (with iron) can reversibly bind one molecule of oxygen Forms oxyhemoglobin (HbO2) (bright red) Deoxyhemoglobin when not binding O2 (dark red)

19. Figure 17.2 4

20. Figure 17.2 5 The quaternary structure of hemoglobin β chain 1 α chain 1 Heme β chain 2 α chain 2

21. Figure 17.2 6 The chemical structure of a heme unit Heme

22. Module 17.2 Review a. Define rouleaux. b. Describe hemoglobin. c. Compare oxyhemoglobin with deoxyhemoglobin.

23. Module 17.3: Red blood cell production and recycling RBC production and recycling Events occurring in red bone marrow Blood cell formation (erythropoiesis) occurs only in red bone marrow (myeloid tissue) Located in vertebrae, ribs, sternum, skull, scapulae, pelvis, and proximal limb bones Fatty yellow bone marrow can convert to red bone marrow in cases of severe, sustained blood loss Developing RBCs absorb amino acids and iron from bloodstream and synthesize Hb

24. Module 17.3: Red blood cell production and recycling Events occurring in red bone marrow (continued) Stages Proerythroblasts Erythroblasts Actively producing Hb After four days becomes normoblast Reticulocyte (80% of mature cell Hb) Ejects organelles including nucleus Enters bloodstream after two days After 24 hours in circulation, is mature RBC

25. Module 17.3: Red blood cell production and recycling Events occurring at macrophages Engulf old RBCs before they rupture (hemolyze) Hemoglobin recycling Iron Stored in phagocyte Released into bloodstream attached to plasma protein (transferrin) Globular proteins disassembled into amino acids for other uses Heme  biliverdin bilirubin bloodstream Hemoglobin not phagocytized breaks down into protein chains and eliminated in urine (hemoglobinuria)

26. Module 17.3: Red blood cell production and recycling Events occurring at liver Bilirubin excreted into bile Accumulating bile due to diseases or disorders can lead to yellowish discoloration of eyes and skin (jaundice) Events occurring at the large intestine Bacteria convert bilirubin to urobilins and stercobilins which become part of feces Give feces yellow-brown or brown coloration

27. Module 17.3: Red blood cell production and recycling Events occurring at kidneys Excrete some hemoglobin and urobilins Give urine its yellow color Presence of intact RBCs in urine (hematuria) Only after urinary tract damage

28. Figure 17.3 Events Occurring in the Red Bone Marrow Developing RBCs absorb amino acids and Fe2+ from the bloodstream and synthesize new Hb molecules. Cells destines to become RBCs first differentiate into proerythroblasts. Start Proerythroblasts then differentiate into various stages of cells called erythroblasts, which actively synthesize hemoglobin. Erythroblasts are named according to total size, amount of hemoglobin present, and size and appearance of the nucleus. Events in the life cycle of RBCs Macrophages in liver, spleen, and bone marrow Events Occurring in Macrophages Fe2+ transported in circulation by transferrin Fe2+ RBC formation Amino acids Heme Average life span of RBC is 120 days 90% Biliverdin After roughly four days of differentiation, the erythroblast, now called a normoblast, sheds its nucleus and becomes a reticulocyte (re-TIK-ū-lō-sīt), which contains 80 percent of the Hb of mature RBC. Old and damaged RBCs Bilirubin 10% In the bloodstream, the rupture of RBCs is called hemolysis. Ejection of nucleus After two days in the bone marrow, reticulocytes enter the bloodstream. After 24 hours in circulation, the reticulocytes complete their maturation and become indistinguishable from other mature RBCs. Bilirubin bound to albumin in bloodstream Hemoglobin that is not phagocytized breaks down, and the alpha and beta chains are eliminated in urine. When abnormally large numbers of RBCs break down in the bloodstream, urine may turn red or brown. This condition is called hemoglobobinuria. New RBCs released into circulation Liver Bilirubin Events Occurring in the Kidney Absorbed into the circulation Excreted in bile Hb Events Occurring in the Liver Urobilins Urobilins, sterconilins Bilirubin Eliminated in feces Eliminated in urine Events Occurring in the Large Intestine

29. Module 17.3 Review a. Define hemolysis. b. Identify the products formed during the breakdown of heme. c. In what way would a liver disease affect the level of bilirubin in the blood?

30. Module 17.4: Blood types Blood types Determined by presence or absence of cell surface markers (antigens) Are genetically determined glycoproteins or glycolipids Can trigger a protective defense mechanism (immune response) Identify blood cells as “self” or “foreign” to immune system More than 50 blood cell surface antigens exist Three particularly important A, B, Rh (or D)

31. Module 17.4: Blood types Four blood types (AB antigens) Type A (A surface antigens) Anti-B antibodies in plasma Type B (B surface antigens) Anti-A antibodies in plasma Type AB (Both A and B surface antigens) No anti-A or anti-B antibodies in plasma Type O (no A or B surface antigens) Both anti-A and anti-B antibodies in plasma

32. Figure 17.4 1 The characteristics of blood for each of the four blood types Type O Type B Type A Type AB Type AB blood has RBCs with both A and B surface antigens. Type B blood has RBCs with surface antigen B only. Type O blood has RBCs lacking both A and B surface antigens. Type A blood has RBCs with surface antigen A only. Surface antigen B Surface antigen A If you have Type A blood, your plasma contains anti-B antibodies, which will attack Type B surface antigens. If you have Type O blood, your plasma contains both anti-A and anti-B antibodies. If you have Type AB blood, your plasma has neither anti-A nor anti-B antibodies. If you have Type B blood, your plasma contains anti-A antibodies.

33. Module 17.4: Blood types Rh surface antigens Separate antigen from A or B Presence or absence on RBC determines positive or negative blood type respectively Examples: AB+, O–

34. Figure 17.4 3

35. Module 17.4: Blood types Antigen-antibody interactions Antibodies “protect our bodies” from “foreign” blood cells Anti-A and anti-B antibodies remain constant through life while anti-Rh antibodies can develop for Rh– people If one blood type is exposed to corresponding antibodies, clumping (agglutination) occurs Hemolysis may occur Cross-reactions (transfusion reactions) can block blood vessels to vital organs with agglutinatedRBCs or cell fragments Important to make sure donor and recipient blood types are compatible (will not cross-react)

36. Figure 17.4 2 The events in a cross-reaction between incompatible donor and recipient blood types RBC Agglutination (clumping) Hemolysis Opposing antibodies Surface antigens

37. Figure 17.4 4 Results of blood typing tests on blood samples from four individuals Blood type Anti-B Anti-D Anti-A A+ B+ AB+ O–

38. Module 17.4 Review a. What is the function of surface antigens on RBCs? b. Which blood type(s) can be safely transfused into a person with Type O blood? c. Why can’t a person with Type A blood safely receive blood from a person with Type B blood?

39. CLINICAL MODULE 17.5: Newborn hemolytic disease Newborn hemolytic disease Genetically determined antigens mean that a child can have a blood type different from either parent During pregnancy, the placenta restricts direct transport between maternal and infant blood Anti-A and anti-B antibodies are too large to cross Anti-Rh antibodies can cross Can lead to mother’s antibodies attacking fetal RBCs

40. CLINICAL MODULE 17.5: Newborn hemolytic disease First pregnancy with Rh– mother and Rh+ infant During pregnancy, few issues occur because no anti-Rh antibodies exist in maternal circulation During birth, hemorraging may expose maternal blood to fetal Rh+ cells Leads to sensitization or activation of mother’s immune system to produce anti-Rh antibodies

41. Figure 17.5 Rh– mother First Pregnancy of an Rh– Mother with an Rh+ infant Rh+ fetus The most common form of hemolytic disease of the newborn develops after an Rh– women has carried an Rh+ fetus. During First Pregnancy Problems seldom develop during a first pregnancy, because very few fetal cells enter the maternal circulation then, and thus the mother’s immune system is not stimulated to produce anti-Rh antibodies. Maternal blood supply and tissue Placenta Fetal blood supply and tissue Exposure to fetal red blood cell antigens generally occurs during delivery, when bleeding takes place at the placenta and uterus. Such mixing of fetal and maternal blood can stimulate the mother’s immune system to produce anti-Rh antibodies, leading to sensitization. Hemorrhaging at Delivery Maternal blood supply and tissue Rh antigen on fetal red blood cells Fetal blood supply and tissue Roughly 20 percent of Rh– mothers who carried Rh+ children become sensitized within 6 months of delivery. Because the anti-Rh antibodies are not produced in significant amounts until after delivery, a woman’s first infant is not affected. Maternal Antibody Production Maternal antibodies to Rh antigen Maternal blood supply and tissue

42. CLINICAL MODULE 17.5: Newborn hemolytic disease Second pregnancy with Rh– mother and Rh+ infant Subsequent pregnancy with Rh+ infant can allow maternal anti-Rh antibodies to cross placental barrier Attack fetal RBCs and cause hemolysis and anemia = Erythroblastosis fetalis Full transfusion of fetal blood may be necessary to remove maternal anti-Rh antibodies Prevention RhoGAM antibodies can be administered to maternal circulation at 26–28 weeks and before/after birth Destroys any fetal RBCs that cross placenta Prevents maternal sensitization

43. Figure 17.5 Rh– mother Second Pregnancy of an Rh– Mother with an Rh+ Infant Rh+ fetus If a subsequent pregnancy involves an Rh+ fetus, maternal anti-Rh antibodies produced after the first delivery cross the placenta and enter the fetal bloodstream. These antibodies destroy fetal RBCs, producing a dangerous anemia. The fetal demand for blood cells increases, and they begin leaving the bone marrow and entering the bloodstream before completing their development. Because these immature RBCs are erythroblasts, HDN is also known as erythroblastosis fetalis. Fortunately, the mother’s anti-Rh antibody production can be prevented if such antibodies (available under the name RhoGAM) are administered to the mother in weeks 26–28 of pregnancy and during and after delivery. These antibodies destroy any fetal RBCs that cross the placenta before they can stimulate a maternal immune response. Because maternal sensitization does not occur, no anti-Rh antibodies are produced. During Second Pregnancy Maternal blood supply and tissue Maternal anti-Rh antibodies Fetal blood supply and tissue Hemolysis of fetal RBCs

44. CLINICAL MODULE 17.5 Review a. Define hemolytic disease of the newborn (HDN). b. Why is RhoGAM administered to Rh– mothers? c.Does an Rh+ mother carrying an Rh– fetus require a RhoGAM injection? Explain your answer.

45. Module 17.6: White blood cells White blood cells (leukocytes) Spend only a short time in circulation Mostly located in loose and dense connective tissues where infections often occur Can migrate out of bloodstream Contact and adhere to vessel walls near infection site Squeeze between adjacent endothelial cells = Emigration or diapedesis Are attracted to chemicals from pathogens, damaged tissues, or other WBCs = Positive chemotaxis

46. Module 17.6: White blood cells White blood cell types Granular leukocytes (have cytoplasmic granules) Neutrophil Eosinophil Basophil Agranular leukocytes (lacking cytoplasmic granules) Monocyte Lymphocyte Changing populations of different WBC types associated with different conditions can be seen in a differential WBC count

47. Module 17.6: White blood cells Granular leukocytes Neutrophils Multilobed nucleus Phagocytic cells that engulf pathogens and debris Eosinophils Granules generally stain bright red Phagocytic cells that engulf antibody-labeled materials Increase abundance with allergies and parasitic infections Basophils Granules generally stain blue Release histamine and other chemicals promoting inflammation

48. Figure 17.6 The structure and function of white blood cells (leukocytes) GRANULAR LEUKOCYTES Neutrophil Eosinophil Basophil WBCs can be divided into two classes Shared Properties of WBCs AGRANULAR LEUKOCYTES • WBCs circulate for only a short portion of their life span, using the bloodstream primarily to travel between organs and to rapidly reach areas of infection or injury. White blood cells spend most of their time migrating through loose and dense connective tissues throughout the body. Monocyte Lymphocyte • All WBCs can migrate out of the bloodstream. When circulating white blood cells in the bloodstream become activated, they contact and adhere to the vessel walls and squeeze between adjacent endothelial cells to enter the surrounding tissue. This process is called emigration, or diapedesis (dia, through; pedesis, a leaping). • All WBCs are attracted to specific chemical stimuli. This characteristic, called postive chemotaxis (kē-mō-TAK-sis), guides WBCs to invading pathogens, damaged tissues, and other active WBCs. • Neutrophils, eosinophils, and monocytes are capable of phagocytosis. These phagocytes can engulf pathogens, cell debris, or other materials. Macrophages are monocytes that have moved out of the bloodstream and have become actively phagocytic.

49. Module 17.6: White blood cells Agranular leukocytes Monocytes Large cells with bean-shaped nucleus Enter tissues and become macrophages (phagocytes) Lymphocytes Slightly larger than RBC with large round nucleus Provide defense against specific pathogens or toxins

50. Module 17.6 Review a. Identify the five types of white blood cells. b. Which type of white blood cell would you find in the greatest numbers in an infected cut? c. How do basophils respond during inflammation?