Hemo, hemato refers to blood Many human rituals involve blood. Recognized as essential to life. Hemo, hemato = blood. Hemo, hemato refers to blood

Characteristics of Blood Fluid; connective tissue Living cells = formed elements Non-living matrix = plasma Transport - Gases, nutrients, wastes, hormones, heat Regulation Defense Blood cells - 45% plasma - 55% formed elements Buffy layer = WBC, platelets More viscous than water. Viscosity important b/c affects load on heart, ease of pumping through small blood vessels. 5 liters per adult. 8% of body weight. Important organ FUNCTI”ONS; transport, as noted. Blood temperature is slightly higher than body temperature Regulation of salt, sollute concentrations, pH of body fluids. pH must remain between 7.35–7.45 Protection: clotting to stop blood loss against pathogens. WBC phagocytize bacteria, produce antibodes, interferons, complement proteins. Important part of inflammatory response.

Blood Plasma about 90 percent water Includes dissolved substances: Nutrients Salts (metal ions) Respiratory gases Hormones Proteins Waste products Blood Plasma makes up 55% of blood volume. Composed of approximately 90 percent water Includes many dissolved substances Nutrients - glucose, amino acids, fatty acids, vitamins Salts (metal ions) - Na+, K+, Ca++, Mg++, Cl-, H2CO3. Blood buffering, membrane permeability. Respiratory gases- ; Hormones Proteins - most abundant component. Albumin: helps maintain osmotic pressure, retain water in blood. globulins: bind to cpds, for transport. Ex. LDL, HDL. Gamma globulins for defense. Clotting proteins: stop blood loss when vessel is broken. Antibodies - protect from pathogens. Proteins are NOT used as fuel source by cells. Waste products - urea.

Formed Elements Erythrocytes = red blood cells, RBC Leukocytes = white blood cells, WBC Platelets = cell fragments RBC 45% WBC 1% Platelets - essential to clotting

Erythrocytes (Red Blood Cells) Carry oxygen Biconcave disks Essentially bags of hemoglobin Anucleate (no nucleus) Contain very few organelles Outnumber white blood cells 1000:1 Hematocrit - % RBC Also carry some carbon dioxide, small amount. Shape produces large surface/volume, so well suited for gas exchange. Hemoglobin - Iron-containing protein Binds strongly, but reversibly, to oxygen. Bright red when bound. Each hemoglobin molecule has four oxygen binding sites. Dependent on iron in heme group. Each erythrocyte has 300 million hemoglobin molecules = 1.2 billion O2 per RBC. Few organelles - no mitochondria, so no aerobic respiration. Use glycolysis alone for energy. Do not use up any of the O2 they shuttle. No nucleus, th4, no going back to genome for different products. Must make do with whatever RNA it has. Density ranges of RBC - 4-6 million per mm3 hematocrit reflects oxygen-carrying capacity of blood. Too low = anemia. Too high = polycythemia. If viscosity is too high, can cause high BP. At high altitudes, more RBC made after 3 days. Reflects need of body for more oxygen.

Fate of Erythrocytes Unable to divide, grow, or synthesize proteins Wear out in 100 to 120 days then eliminated by phagocytes in spleen or liver RBCs replaced by dividing stem cells Blood stem cells = hemocytoblasts. Worn out cell parts are recycled; iron goes to bone marrow, heme group converted to bilirubin in liver and into bile duct, out w/ food waste. Sequence of colors of a healing bruise due to conversion of hemoglobin to bilirubin. Jaundice (yellow skin color) due to excess bilirubin in circulation. Caused by bile duct is blocked or massive breakdown of RBCs.

Control of Erythrocyte Production Homeostasis triggered by blood oxygen levels Kidneys produce erythropoietin as a response to reduced oxygen levels in the blood RBC replaced at typical rate of 2 million per sec just to maintain base level. Erythropoietin stimulates stem cells in red bone marrow to divide. Blood doping - using erythropoietin or synthetic version to increase RBC content. Dangerous risk of clotting, high BP with excess RBC.

Hematopoiesis In red bone marrow RBCs, WBCs Blood cell formation Occurs in red bone marrow: long bones in children, hip (iliac) in adults. All blood cells are derived from a common stem cell (hemocytoblast). Good example of why stem cells in general are valued for medical purposes. Analogy with trip across US, no backtracking allowed. Hemocytoblast differentiation Lymphoid stem cell produces lymphocytes Myeloid stem cell produces other formed elements Classification based on appearance when stained. Granules become visible. Maturation in bone marrow, mostly. Lifespans vary from days to years, dept on type of WBC. WBC can leave the blood vessel, move btw tissues and enter lymph system.

Leukocytes (White Blood Cells) Body’s defense against disease Has nucleus and organelles moves into and out of blood vessels (diapedesis) moves by amoeboid motion responds to chemicals from damaged tissues Moves to site of tissue damage via circulatory system, then leaves capillaries and moves like an amoeba thru tissues. Chemotaxis - responds to chemicals. Immune and inflammatory responses lifespan from days to years, dept on type. Normal levels are between 4,000 and 11,000 cells per millimeter Abnormal leukocyte levels Leukocytosis - above 11,000 leukocytes/ml Generally indicates an infection. When needed, body doubles production of WBCs. Leukopenia - Abnormally low leukocyte level Commonly caused by certain drugs Leukemia - “white blood” cancerous bone marrow produces lots more WBCs. Immature and not able to function as defense for body. Treatment can involve bone marrow transplant.

Granulocytes 1. Neutrophils Multilobed nucleus with fine granules Act as phagocytes at active sites of infection 2. Eosinophils - Large brick-red cytoplasmic granules Found in response to allergies and parasitic worms 3. Basophils - Have histamine-containing granules Initiate inflammation Granulocytes - W/ granules in their cytoplasm = vesicles that contain proteins, enzymes. 1.neutrophils, - about half of WBC. phagocytosis, esp agst bact and some fungi. Can increase in number during infection. First line of defense. 2. Eosinophils - rare. Only 2-3% of WBC. Conduct chemical attack agst large pathogens, moderate response to allergens. 3. Basophils - rarest WBC only 0.5% of WBC. Release histamine when tissue is damaged. Histamine causes more blood plasma to be released. Brings nutrients for repair and swelling, redness to tissue. Inflammatory response that leads to healing. Trigger for allergies.

Agranulocytes Lymphocytes (B, T cells) Large nucleus Specific immune response Monocytes Largest of the white blood cells Function as macrophages Important in fighting chronic infection Lymphocytes - 30% of WBC. In blood stream, lymph nodes, spleen, thymus gland. Part of immune response that recognizes specific threats. Vaccines stimulate their production. B cells give rise to antibodies. T cells destroy specific threats of virus, bact, cancer cells. Monocytes - leave blood vessels and become larger macrophages, eating up pathogens, esp viruses and bacteria. Can stimulate production of lymphocytes.

leukemia

Platelets Derived from ruptured multinucleate cells (megakaryocytes) Needed for the clotting process Normal platelet count = 300,000/mm3 Platelets are fragments of cell, pinched off from megakaryocytes by the thousands. Megakaryocytes stay in bone marrow. Carry fluids that are sealed off from blood fluids. Platelets last only a few days, then must be replaced. Continuous. Platelet concentration can be increased by hormone thrombopoietin.

Hemostasis = Stoppage of blood flow Result of a break in a blood vessel Fast reaction - 3-6 minutes 3 phases Fast reaction to prevent loss of blood. Whole process takes only 3-6 minutes.

1. Vascular Spasms spasm by blood vessel muscles blood vessel narrows, decreasing blood loss Other factors which contribute to vascular spasm: activation of pain receptors direct injury to smooth muscle cells. Serotonin causes spasms. Released by bound platelets. Spasms can last up to 30 minutes.

2. Platelet Plug Formation Collagen fibers exposed Platelets become “sticky” and cling to fibers release chemicals to attract more platelets Platelets form a plug Platelet plug formation: Collagen fibers are exposed by a break in a blood vessel Platelets become “sticky” and cling to fibers Anchored platelets release chemicals to attract more platelets Platelets pile up to form a platelet plug. With minor injuries, that may be all; no blood clot. If bigger injury, clot forms.

3. Coagulation a clotting cascade Injured tissues stimulate release of prothrombin activator Which (with Ca++) converts prothrombin to thrombin (an enzyme) Thrombin joins fibrinogen proteins into hair-like fibrin. Network that traps cells. Process also involves vitamin K, other blood protein clotting factors, thromboplastin Chain of activation events, some involving enzymes. At least 12 clotting factors needed. Damaged vessels & platelets release thromboplastin, which causes release of prothrombin activator. With Ca++ present, Prothrombin activator converts prothrombin to thrombin (an enzyme). Fibrinogen is soluble in plasma. Fibrin is not. Network traps RBCs, platelets; plug stops blood flow. All in under an hour.

Coagulation Fibrin forms a meshwork (the basis for a clot) BLOOD Clotting - Blood usually clots within 3 to 6 minutes. First fibrin tangles in less than a minute. Platelets contract, tightening clot. Requires 12 different factors. The clot remains as endothelium regenerates The clot is broken down after tissue repair Hemophilia - lack of blood clotting. Most common form is hemo a, which lacks Factor VIII. Treatment now with addition of GE protein factors. Minor injuries can be life threatening. Puts lots of blood in interstitial spaces. Causes joint problems. Aspirin - inhibits clotting reaction by slowing platelet plug. Avoid before surgery.

Undesirable Clotting Thrombus A clot in an unbroken blood vessel Embolus A thrombus that breaks away and floats freely in the bloodstream Bleeding Disorders Hemophilia, thrombocytopenia Thrombus A clot in an unbroken blood vessel Can be deadly in areas like the heart Embolus A thrombus that breaks away and floats freely in the bloodstream Can later clog vessels in critical areas such as the brain BLEEDING DISORDERS Thrombocytopenia - deficiency of platelets due to suppression of myeloid tissue in the bone marrow. Can also be caused by liver that doesn’t make adequate clotting factors. Needs enough Vit K to make clotting factors. Sick liver, as with cirrhosis, hepatitis is not easily treated.

Blood Groups and Transfusions Large losses of blood: consequences Loss of 15 to 30 percent causes weakness Loss of over 30 percent causes shock, which can be fatal Transfusions to replace blood quickly must be same blood group

Blood contains genetically determined proteins A foreign protein (antigen) may be attacked by the immune system There are over 30 common red blood cell antigens The most vigorous transfusion reactions are caused by ABO and Rh blood group antigens Describe antigen/antibody production, prelude to immune system.

Blood is “typed” by using antibodies that will cause blood cells to clump (agglutination) Based on the presence or absence of two antigens Type A Type B The lack of these antigens is called type O Blood samples are mixed with anti-A and anti-B serum Coagulation or no coagulation leads to determining blood type Typing for ABO and Rh factors is done in the same manner Cross matching – testing for agglutination of donor RBCs by the recipient’s serum, and vice versa

Blood Typing If transfusion with wrong type of blood, clumping occurs. Vessels clogged, foreign RBCs broken down, release hemoglobin - LOTS of hemoglobin. Clogs kidney tubules, shuts down kidneys. Fatal. Figure 10.8

Rh Blood Groups Named for one of eight Rh antigens (agglutinogen D) Most Americans are Rh+ Problems can occur in mixing Rh+ blood into a body with Rh– blood Rxn does not occur right away, as Rh antibodies are not made unless exposure has occurred.

Danger is only when the mother is Rh– and the father is Rh+, and the child inherits the Rh+ factor The mismatch of an Rh– mother carrying an Rh+ baby can cause problems for the unborn child The first pregnancy usually proceeds without problems The immune system is sensitized after the first pregnancy In a second pregnancy, the mother’s immune system produces antibodies to attack the Rh+ blood (hemolytic disease of the newborn) Same problem if several transfusions are given, Rh- to Rh+. Prevent problem by treating Rh+ mother with antibody Rhogam to reduce concentration of inciting antigen. So mother’s immune system never sees

Developmental Aspects of Blood Sites of blood cell formation fetal liver, spleen are early sites of blood cell formation Bone marrow takes over hematopoiesis by the seventh month Fetal hemoglobin differs from hemoglobin produced after birth Fetal hemoglobin w/ higher affinity for oxygen. Helps to maintain enough O2 in fetus. Switches after birth to adult
alpha, beta forms. Rapic breakdown of fetal hemglbn can lead to a form of jaundice (physiological jaundice) if the liver cannot process the fetal hemoglbn fast enough. treatment of sickle cell involves stimulating the production of fetal hmg, as this is less subject to sickling.

Blood Disorders Carbon monoxide poisoning Anemia - reduced oxygen capacity Leukemia - excess WBC Mononucleosis - viral infection Blood poisoning CO poisoning - colorless, odorless gas. From any burning of carbon. 200 times higher affinity for hemoglobin than oxygen. Displaces it in heme group and stays there for hours. Treatment - fresh air, transfusion. Use CO detector indoors. Anemia - several causes, common result is low oxygen capacity. Iron deficiency. Fewer heme groups. Most common world wide. Aplastic anemia - not enough stem cells in bone marrow. Sickle cell anemia - Leukemia - excess WBC. Several types, common symptom is lots of immature WBC circulating which prevents normal functioning of other BC, including RBC. Treatments involve killing rapidly dividing cells, which kills own stem cells. Then replace with matched donor marrow. Mononucleosis caused by Epstein Barr virus. Can be transmitted person to person. Must let body fight off infection takes weeks. No magic pill.