Artery White blood cells Platelets Red blood cells

Artery White blood cells Platelets Red blood cells

• Deliver O 2 • Remove metabolic wastes • Maintain temperature, p. H, and fluid volume • Protection from blood loss- platelets • Prevent infection- antibodies and WBC • Transport hormones

Plasma-55% Buffy coat-<1% Formed elements-45%

90% Water 8% Solutes: • Proteins Albumin (60 %) Alpha and Beta Globulins Gamma Globulins fibrinogens • Gas • Electrolytes

• Organic Nutrients Carbohydrates Amino Acids Lipids Vitamins • Hormones • Metabolic waste CO 2 Urea

• Leukocytes • Platelets

• Erythrocytes (red blood cells) • Leukocytes (white blood cells) • Platelets (thrombocytes)

Erythrocytes

Erythrocyte 7. 5 m in dia · Anucleate- so can't reproduce; however, repro in red bone marrow · Hematopoiesis- production of RBC · Function- transport respiratory gases · Hemoglobin- quaternary structure, 2 chains and 2 chains · Lack mitochondria. Why? · 1 RBC contains 280 million hemoglobin molecules · Men- 5 million cells/mm 3 · Women- 4. 5 million cells/mm 3 · Life span 100 -120 days and then destroyed in spleen (RBC graveyard)

Hemoglobin

Hematopoiesis • Hematopoiesis (hemopoiesis): blood cell formation – Occurs in red bone marrow of axial skeleton, girdles and proximal epiphyses of humerus and femur

Hematopoiesis • Hemocytoblasts (hematopoietic stem cells) – Give rise to all formed elements – Hormones and growth factors push the cell toward a specific pathway of blood cell development • New blood cells enter blood sinusoids

Erythropoiesis • Erythropoiesis: red blood cell production – A hemocytoblast is transformed into a proerythroblast – Proerythroblasts develop into early erythroblasts

Erythropoiesis – Phases in development 1. Ribosome synthesis 2. Hemoglobin accumulation 3. Ejection of the nucleus and formation of reticulocytes – Reticulocytes then become mature erythrocytes

Stem cell Hemocytoblast Committed cell Developmental pathway Proerythroblast Early Late erythroblast Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus Normoblast Reticulo- Erythrocyte Figure 17. 5

Regulation of Erythropoiesis • Too few RBCs leads to tissue hypoxia • Too many RBCs increases blood viscosity • Balance between RBC production and destruction depends on – Hormonal controls – Adequate supplies of iron, amino acids, and B vitamins

Hormonal Control of Erythropoiesis • Erythropoietin (EPO) – Direct stimulus for erythropoiesis – Released by the kidneys in response to hypoxia

Hormonal Control of Erythropoiesis • Causes of hypoxia – Hemorrhage or increased RBC destruction reduces RBC numbers – Insufficient hemoglobin (e. g. , iron deficiency) – Reduced availability of O 2 (e. g. , high altitudes)

Hormonal Control of Erythropoiesis • Effects of EPO – More rapid maturation of committed bone marrow cells – Increased circulating reticulocyte count in 1 – 2 days • Testosterone also enhances EPO production, resulting in higher RBC counts in males

Formation & Destruction of RBCs

Blood Cell Production

RBC Diseases Anemia- when blood has low O 2 carrying capacity; insufficient RBC or iron deficiency. Factors that can cause anemia- low iron, B 12 deficiency

RBC Diseases Sickle-cell anemia- • Hb. S results from a change in just one of the 287 amino acids in the chain in the globin molecule. • Found in 1 out of 400 African Americans. • Homozygous for sickle-cell is deadly, but in malaria infested countries, the heterozygous condition is beneficial.

RBC Diseases Polycythemia- excess of erythrocytes, viscosity of blood; 8 -11 million cells/mm 3 Usually caused by cancer; however, naturally occurs at high elevations Blood doping- in athletes remove blood 2 days before event and then replace it- banned by Olympics.

4, 000 -11, 000 cells/mm 3 Never let monkeys eat bananas Granulocytes Neutrophils- 40 -70% Eosinophils- 1 -4% Basophils- <1% Agranulocytes Monocytes- 4 -8% Lymphocytes- 20 -45%

Basophil Eosinophil Lymphocyte platelet Neutrophil Monocyte

ID WBC’s

White Blood Cells • Protect body against microorganisms and remove dead cells and debris • Movements Ameboid Diapedesis Chemotaxis Passive Immunity Active Immunity Antigen – Antibody

What do T- and B-cells do? Above show T cells http: //www. sciencemuseum. org. uk/whoami/findoutmore/yourbody/whatdo esyourimmunesystemdo/howdoesyourimmunesystemwork/whatdot-andbcellsdo. aspx T- and B-cells are highly specialized defender cells - different groups of cells are tailored to different germs. When your body is infected with a particular germ, only the T- and Bcells that recognize it will respond. These selected cells then quickly multiply, creating an army of identical cells to fight the infection. Special types of T- and B-cells 'remember' the invader, making you immune to a second attack.

Left shows T cells top and E-Coli below T- and B-cells recognize invaders by the shape of molecules - antigens on their surfaces. Your immune system can produce a T- and B-cell to fit every possible shape. However, any T- or B-cell that recognized molecules found on your cells were destroyed while you were growing in the womb, to prevent them from attacking your own body. But you were left with millions of others, one for every foreign antigen you might ever encounter.

Left shows T cell (orange) attacking a cancer cell http: //www. sciencemuseum. org. uk/whoami/findoutmore/your body/whatdoesyourimmunesystemdo/howdoesyourimmunes ystemwork/whatdot-andb-cellsdo. aspx Having recognized the invader, different types of T-cell then have different jobs to do. Some send chemical instructions (cytokines) to the rest of the immune system. Your body can then produce the most effective weapons against the invaders, which may be bacteria, viruses or parasites. Other types of Tcells recognize and kill virus-infected cells directly. Some help B-cells to make antibodies, which circulate and bind to antigens.

Left shows the molecular structure of an antibody. http: //www. sciencemuseum. org. uk/whoami/findoutmore/yourbody/whatdoesy ourimmunesystemdo/howdoesyourimmunesystemwork/whatdot-andbcellsdo. aspx With the help of T-cells, Bcells make special Y-shaped proteins called antibodies. Antibodies stick to antigens on the surface of germs, stopping them in their tracks, creating clumps that alert your body to the presence of intruders. Your body then starts to make toxic substances to fight them. Patrolling defender cells called phagocytes engulf and destroy antibody-covered intruders

Leukocyte Squeezing Through Capillary Wall WBCs Moving out of the blood stream

• Leukopenia • • Abnormally low WBC count—drug induced Leukemias • Cancerous conditions involving WBCs • Named according to the abnormal WBC clone involved • Mononucleosis • highly contagious viral disease caused by Epstein-Barr virus; excessive # of agranulocytes; fatigue, sore throat, recover in a few weeks

White Blood Cells Types Neutrophils: Most common; phagocytic cells destroy bacteria (60%) Eosinophils: Detoxify chemicals; reduce inflammation (4%) Basophils: Alergic reactions; Release histamine, heparin increase inflam. response (1%) Lymphocytes: Immunity 2 types; b & t Cell types. Ig. G-infection, Ig. M-microbes, Ig. A-Resp & GI, Ig. EAlergy, Ig. D-immune response Monocytes: Become macrophages

Platelets • Small fragments of megakaryocytes • Formation is regulated by thrombopoietin • Blue-staining outer region, purple granules • Granules contain serotonin, Ca 2+, enzymes, ADP, and platelet-derived growth factor (PDGF)

Stem cell Developmental pathway Hemocytoblast Promegakaryocyte Megakaryoblast Megakaryocyte Platelets Figure 17. 12

Hemostasis- stoppage of bleeding Platelets: 250, 000 -500, 000 cells/mm 3 Tissue Damage Platelet Plug Clotting Factors

Hemostasis: 1. Vessel injury 2. Vascular spasm 3. Platelet plug formation 4. Coagulation

Hemostasis (+ feedback) Clotting Factors thromboplastin Prothrombin Thrombin Fibrinogen Fibrin Traps RBC & platelets Platelets release thromboplastin

Blood Clot RBC Does this look like spider webs? Platelet Fibrin thread

Disorders of Hemostasis • Thromboembolytic disorders: undesirable clot formation • Bleeding disorders: abnormalities that prevent normal clot formation

Thromboembolytic Conditions • Thrombus: clot that develops and persists in an unbroken blood vessel – May block circulation, leading to tissue death • Embolus: a thrombus freely floating in the blood stream – Pulmonary emboli impair the ability of the body to obtain oxygen – Cerebral emboli can cause strokes

Thromboembolic Conditions • Prevented by – Aspirin • Antiprostaglandin that inhibits thromboxane A 2 – Heparin • Anticoagulant used clinically for pre- and postoperative cardiac care – Warfarin • Used for those prone to atrial fibrillation

Thrombocytosis- too many platelets due to inflammation, infection or cancer Thrombocytopenia- too few platelets • causes spontaneous bleeding • due to suppression or destruction of bone marrow (e. g. , malignancy, radiation) – Platelet count <50, 000/mm 3 is diagnostic – Treated with transfusion of concentrated platelets

• Impaired liver function – Inability to synthesize procoagulants – Causes include vitamin K deficiency, hepatitis, and cirrhosis – Liver disease can also prevent the liver from producing bile, impairing fat and vitamin K absorption

• Hemophilias include several similar hereditary bleeding disorders • Symptoms include prolonged bleeding, especially into joint cavities • Treated with plasma transfusions and injection of missing factors

Hemophiliac- a sex-linked recessive trait, primarily carried by males (x chromosome)

Type A Type B Type AB Type O

Blood type is based on the presence of 2 major antigens in RBC membranes-- A and B Blood type Antigen Antibody A A anti-B B B anti-A A&B AB no anti body Neither A or B O anti-A and anti-B Antigen- protein on the surface of a RBC membrane Antibody- proteins made by lymphocytes in plasma which are made in response to the presence of antigens. They attack foreign antigens, which result in clumping (agglutination)

Type A b b b b

Type B a a a a

Type O a b a a b b

Type AB

Rh Factor and Pregnancy RH+ indicates protein RH- indicates no protein

Rh Factor and Pregnancy Rh+ mother w/Rh- baby– no problem Rh- mother w/Rh+ baby– problem Rh- mother w/Rh- father– no problem Rh- mother w/Rh- baby-- no problem Rho. GAM used @ 28 weeks

Type AB- universal recipients Type O- universal donor Rh factor: Rh+ 85% dominant in pop Rh- 15% recessive Blood Type Clumping Antibody A antigen A anti-A serum antibody anti-b B antigen B anti-B serum antibody anti-a AB antigen A & B anti A & B serum O neither A or B no clumping w/ either anti A or B anti-a, anti-b -

Blood being tested Type AB (contains agglutinogens A and B; agglutinates with both sera) Anti-A Serum Anti-B RBCs Type A (contains agglutinogen A; agglutinates with anti-A) Type B (contains agglutinogen B; agglutinates with anti-B) Type O (contains no agglutinogens; does not agglutinate with either serum) Figure 17. 16

Blood Type & Rh How Many Have It O O A A B B AB AB 1 person in 3 1 person in 15 1 person in 3 1 person in 16 1 person in 12 1 person in 67 1 person in 29 1 person in 167 Rh Positive Rh Negative Frequency 37. 4% 6. 6% 35. 7% 6. 3% 8. 5% 1. 5% 3. 4%. 6%

ABO Blood Types Phenotype Genotype O i i A I A or I A i B I B or I B i AB IA IB

Punnett square Type A and Type B cross IA IA IB i I AI B I Ai