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Blood

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Considered a connective tissue 5-6L in males, 4-5L in females

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Formed Elements

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RBC, WBC, platelets

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Plasma

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Water with over 100 solutes in it Nutrients, gases, hormones, synthesized cellular products (proteins), clotting factors -Albumin -Serum=plasma without clotting factors

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3 Layers Created when Blood Centrifuged

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Plasma Buffy Coat Red Blood Cells

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Hematocrit

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Volume of RBC in sample Male 47%, female 42% +/- 5%

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Formed Elements (Details)

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Erythrocytes, leukocytes, and platelets make up the formed elements Only WBCs are complete cells RBCs have no nuclei or organelles, and platelets are just cell fragments Most formed elements survive in the bloodstream for only a few days Most blood cells do not divide but are renewed by cells in bone marrow

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Erythrocytes

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Transport O2 and CO2 About 45% of blood volume Biconcave discs -Increases surface area Flexible due to spectrin No nucleus in mature cell -More room for hemoglobin (97%)

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Hemoglobin

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Oxyhemoglobin: Hb bound to oxygen -Oxygen loading takes place in the lungs Deoxyhemoglobin: Hb after oxygen diffuses into tissues (reduced Hb) Carbaminohemoglobin: Hb bound to carbon dioxide

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Production of Erythrocytes

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Erythropoiesis -Occurs in red bone marrow --Axial skeleton, girdles and proximal epiphysis of femur and humerus. -Arises from hemopoiteic stem cell (hemogoblast) as all formed elements but what it becomes is up to the type of receptor the stem cell has.

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Erythropoietin

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Hormone produced by kidneys Causes an increase in RBC production Response is to O2 carrying capacity of the blood -O2 carrying capacity dependent on number as well as O2 carrying ability of blood.

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Hormonal Control of Erythropoiesis

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Erythropoietin (EPO) release by the kidneys is triggered by: -Hypoxia due to decreased RBCs -Decreased oxygen availability -Increased tissue demand for oxygen Enhanced erythropoiesis increases the RBC count in circulating blood

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Dietary Requirements of Erythropoiesis

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Erythropoiesis requires: -Proteins, lipids, and carbohydrates -Iron, vitamin B12, and folic acid The body stores iron in Hb (65%), the liver, spleen, and bone marrow Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin

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Fate and Destruction of Erythrocytes

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The life span of an erythrocyte is 100-120 days Old RBCs become rigid and fragile, and their Hb begins to degenerate Dying RBCs are engulfed by macrophages Heme and globin are separated and the iron is salvaged for reuse

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Fate and Destruction of Erythrocytes

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Heme is degraded to a yellow pigment called bilirubin The liver secretes bilirubin into the intestines as bile The intestines metabolize it into urobilinogen This degraded pigment leaves the body in feces, in a pigment called stercobilin

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Fate and Destruction of Erythrocytes

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Globin is metabolized into amino acids and is released into the circulation Hb released into the blood is captured by haptoglobin and phgocytized

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Erythrocyte Disorders

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Anemia: blood has abnormally low oxygen-carrying capacity -It is a symptom rather than a disease itself -Blood oxygen levels cannot support normal metabolism -Signs/symptoms include fatigue, paleness, shortness of breath, and chills

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Anemia: Insufficient Erythrocytes

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Hemorrhagic anemia: result of acute or chronic loss of blood Hemolytic anemia: prematurely ruptured RBCs Aplastic anemia: destruction or inhibition of red bone marrow

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Anemia: Decreased Hemoglobin Content

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Iron-deficiency anemia results from: -A secondary result of hemorrhagic anemia -Inadequate intake of iron-containing foods -Impaired iron absorption Pernicious anemia results from: -Deficiency of vitamin B12 -Lack of intrinsic factor needed for absorption of B12

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Anemia: Abnormal Hemoglobin

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Thalassemias: absent or faulty globin chain in Hb -RBCs are thin, delicate, and deficient in Hb

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Anemia: Abnormal Hemoglobin

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Sickle-cell anemia: results from a defective gene coding for an abnormal Hb called hemoglobin S (HbS) -HbS has a single amino acid substitution in the beta chain -This defect causes RBCs to become sickle-shaped in low oxygen situations

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Polycythemia

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Polycythemia: excess RBCs that increase blood viscosity Three main polycythemias are: -Polycythemia vera -Secondary polycythemia -Blood doping

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Hemostasis response

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Fast, localized and controlled (why is this a good idea?) Involves many factors (enzymes) present in plasma, and substances released by platelets and injured tissue cells.

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Hemostasis response

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These processes begin when the endothelial lining or vascular muscle tissue is disrupted, with the release of chemicals by endothelial cells, or even because of reflexes initiated by local pain receptors.

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Three main steps

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Vascular spasm Platelet plug formation Coagulation (clotting)

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Vascular spasm

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Vasoconstriction (immediate) Not only helps in mechanical restriction of blood loss but allows more time more for "plugging" and clotting to occur.

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Platelet plug formation

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Platelet aggregation forms a temporary "plug" to seal the "break" in tissue. During endothelial damage, underlying collagen fibers get exposed. Aided by a plasma protein called von Wllebrand factor (VWF) platelets attach to these fibers.

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Remember that "spikey" thing in lab?

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Platelets become "sticky" and "spiked" When attached their granules breakdown and begin to release chemicals. -Serotonin (enhances spasms) -ADP (attracts more platelets) -Thrombaxane A2 (helps both above)

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Positive feedback, one of the few in the body. Why is this good news/bad news?

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Platelet aggregation and clotting are great things in an area of injury to prevent blood loss, but clotting is not a great idea in undamaged areas. Even in damaged areas it could be a problem. This helps us understand the new reasoning in ischemic heart disease/MI.

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Inhibition of platelet plug

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Prostacyclin (PGI2), a prostaglandin, is produced by intact endothelial cells, is a strong inhibitor of platelet aggregation. This helps limit the platelet plug to the immediate area.

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Coagulation

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Prothrombin activator needs to be formed. Prothrombin activator converts prothrombin (a plasma protein) into thrombin (an enzyme). Thrombin catalyzes fibrinogen molecules in the plasma to form fibrin mesh which seals the "hole" to allow repair of the damaged vessel.

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What are Factors?

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Substances that ether promote clotting (procoagulants or clotting factors) or inhibit it (anticoagulants) Some are proenzymes (what does this mean?). An important factor is Ca+2 Vitamin K is needed to make four of them

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Blood Factors

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Named by order of discovery. Procoagulants are numbered I-XIII Vitamin K required for the synthesis of four of them made by the liver.

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Anticoagulants

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These predominate in the circulation until vessel injury occurs.

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Phase 1: Two pathways to Prothrombin Activator

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Extrinsic -Clotting initiated by factors released by tissue (or inside the body) Intrinsic -Clotting initiated outside the body (all factors are found in the blood) Most clotting involves both pathways

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Intrinsic

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All factors are found in blood Slower than extrinsic

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Extrinsic

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Started when damaged tissue releases tissue factor (also known as TF or factor III or tissue thromboplastin) This is faster as it bypasses several steps of the intrinsic pathway.

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Both Pathways

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Each pathway requires Ca 2+ Both "cascade" to a common intermediate, factor X. Once activated factor X complexes with Ca 2+ , PF3 and factor V to form prothrombin activator.

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Phase 2: Common pathway to Thrombin

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PT activator catalyzes the plasma protein prothrombin to transform to thrombin, which is an activated enzyme.

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Phase 3: Common pathway to fibrin mesh

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Thrombin catalyzes the polymerization of fibrinogen which begins to form fibrin strands. In the presence of Ca+2 thrombin activates factor XIII (fibrin stabilizing factor) which cross-links fibrin strands together.

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Final Result

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Fibrin mesh is produced.

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Clot retraction and repair

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Contractile proteins in platelets squeeze out plasma, pull strands together. Platelets also release platelet-derived growth factor (PDGF) which causes muscle cells and fibroblasts, to begin to heal the vessel damage. Endothelium repair stimulated by vascular endothelial growth factor (VEGF).

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Fibrinolysis

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Removal of unneeded clots when healing has occurred. Plasmin: digests clots. Produced when plasma protein plasminogen is activated. Endothelial cells around the clot release tissue plasminogen activator (tPA) Plasmin not at clot gets destroyed by enzymes.

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Limiting clot formation

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Thrombin binds to fibrin but thrombin not bound to fibrin gets inactivated by antithrombin III. Protein C Heparin, contained in basophils, mast cells and endothelial cells.

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Prevention of undesirable clotting

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Smooth endothelium -Inflammation -histamine Nitric oxide Prostacyclin Vitamin E quione

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Hemostasis disorders

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Thromboembolic : undesirable clot formation -Thrombus: clot in an undamaged blood vessel -Embolus: clot that breaks free -Embolism: embolus that gets "stuck" and obstructs a vessel Disseminated Intravascular Coagulation -Some blood clots, then the rest doesn't

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Hemostasis disorders

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Bleeding disorders Thrombocytopenia -Low platelet count --petechiae Impaired liver function -Liver can't produce procoagulants -Vitamin K deficiency (rare) -Liver disease (bile not produced, Vit K can't be absorbed since fat can't be absorbed)

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Hemostasis disorders

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Hemophilias: A: Deficiency of Factor VIII B: Deficiency of Factor IX A and B are X chromosome linked Also a C type (Factor XI deficiency) that is seen in both sexes, less severe

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Leukocytes (WBCs)

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Leukocytes, the only blood components that are complete cells: -Are less numerous than RBCs -Make up 1% of the total blood volume -Can leave capillaries via diapedesis -Move through tissue spaces Leukocytosis - WBC count : normal 5,000-10,000 -Over 11,000 / mm3

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Granulocytes

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Granulocytes: neutrophils, eosinophils, and basophils -Contain cytoplasmic granules that stain specifically (acidic, basic, or both) with Wright's stain -Are larger and usually shorter-lived than RBCs -Have lobed nuclei -Are all phagocytic cells

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Neutrophils

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Neutrophils have two types of granules that: - Take up both acidic and basic dyes - Give the cytoplasm a lilac color - Contain peroxidases, hydrolytic enzymes, and defensins (antibiotic-like proteins) Neutrophils are our body's bacteria slayers

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Eosinophils

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Eosinophils account for 1-4% of WBCs - Have red-staining, bilobed nuclei connected via a broad band of nuclear material - Have red to crimson (acidophilic) large, coarse, lysosome-like granules - Lead the body's counterattack against parasitic worms - Lessen the severity of allergies by phagocytizing immune complexes

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Basophils

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Account for 0.5% of WBCs and: - Have U- or S-shaped nuclei with two or three conspicuous constrictions - Are functionally similar to mast cells - Have large, purplish-black (basophilic) granules that contain histamine - Histamine: inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect)

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Agranulocytes

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Agranulocytes: lymphocytes and monocytes: - Lack visible cytoplasmic granules - Are similar structurally, but are functionally distinct and unrelated cell types - Have spherical (lymphocytes) or kidney-shaped (monocytes) nuclei

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Lymphocytes

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Account for 25% or more of WBCs and: - Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm - Are found mostly enmeshed in lymphoid tissue (some circulate in the blood) There are two types of lymphocytes: T cells and B cells - T cells function in the immune response - B cells give rise to plasma cells, which produce antibodies

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Monocytes

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Monocytes account for 4-8% of leukocytes - They are the largest leukocytes - They have abundant pale-blue cytoplasms - They have purple-staining, U- or kidney-shaped nuclei - They leave the circulation, enter tissue, and differentiate into macrophages

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Macrophages

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Macrophages: - Are highly mobile and actively phagocytic - Activate lymphocytes to mount an immune response

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Production of Leukocytes

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Leukopoiesis is stimulated by interleukins and colony-stimulating factors (CSFs) Many hematopoietic hormones are used clinically to stimulate bone marrow

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Formation of Leukocytes

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All leukocytes originate from hemocytoblasts Hemocytoblasts differentiate into myeloid stem cells and lymphoid stem cells Myeloid stem cells become myeloblasts or monoblasts Lymphoid stem cells become lymphoblasts Myeloblasts develop into eosinophils, neutrophils, and basophils Monoblasts develop into monocytes Lymphoblasts develop into lymphocytes

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Leukemia

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Leukemia refers to cancerous conditions involving WBCs Leukemias are named according to the abnormal WBCs involved - Myelocytic leukemia: involves myeloblasts - Lymphocytic leukemia: involves lymphocytes Acute leukemia involves blast-type cells and primarily affects children Chronic leukemia is more prevalent in older people

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Leukemia

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Immature WBCs are found in the bloodstream in all leukemias Bone marrow becomes totally occupied with cancerous leukocytes The WBCs produced, though numerous, are not functional Death is caused by internal hemorrhage and overwhelming infections Treatments include irradiation, antileukemic drugs, and bone marrow transplants

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Blood Transfusions

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Whole blood transfusions are used: - When blood loss is substantial - In treating thrombocytopenia Packed red cells (cells with plasma removed) are used to treat anemia

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Human Blood Groups

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RBC membranes have glycoprotein antigens on their external surfaces These antigens are: - Unique to the individual - Recognized as foreign if transfused into another individual - Promoters of agglutination and are referred to as agglutinogens Presence or absence of these antigens is used to classify blood groups

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Blood Groups

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Humans have 30 varieties of naturally occurring RBC antigens The antigens of the ABO and Rh blood groups cause vigorous transfusion reactions when they are improperly transfused Other blood groups (M, N, Dufy, Kell, and Lewis) are mainly used for legalities

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ABO Blood Groups

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The ABO blood groups consists of: - Two antigens (A and B) on the surface of the RBCs - Two antibodies in the plasma (anti-A and anti-B) ABO blood groups may have various types of antigens and preformed antibodies Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions

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Rh Blood Groups

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There are eight different Rh agglutinogens, three of which (C, D, and E) are common Presence of the Rh agglutinogens on RBCs is indicated as Rh+ Anti-Rh antibodies are not spontaneously formed in Rh- individuals However, if an Rh- individual receives Rh+ blood, anti-Rh antibodies form A second exposure to Rh+ blood will result in a typical transfusion reaction

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Hemolytic Disease of the Newborn

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Hemolytic disease of the newborn - Rh+ antibodies of a sensitized Rh- mother cross the placenta and attack and destroy the RBCs of an Rh+ baby Rh- mother becomes sensitized when exposure to Rh+ blood causes her body to synthesize Rh+ antibodies

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Hemolytic Disease of the Newborn

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The drug RhoGAM can prevent the Rh- mother from becoming sensitized Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth

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Transfusion Reactions

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Transfusion reactions occur when mismatched blood is infused Donor's cells are attacked by the recipient's plasma agglutinins causing: - Diminished oxygen-carrying capacity - Clumped cells that impede blood flow - Ruptured RBCs that release free hemoglobin into the bloodstream

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Transfusion Reactions

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Circulating hemoglobin precipitates in the kidneys and causes renal failure

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Blood Typing

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When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens Positive reactions indicate agglutination

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Plasma Volume Expanders

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When shock is imminent from low blood volume, volume must be replaced Plasma or plasma expanders can be administered

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Plasma Volume Expanders

answer

Plasma expanders - Have osmotic properties that directly increase fluid volume - Are used when plasma is not available - Examples: purified human serum albumin, plasminate, and dextran Isotonic saline can also be used to replace lost blood volume

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Diagnostic Blood Tests

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Laboratory examination of blood can assess an individual's state of health Microscopic examination: - Variations in size and shape of RBCs - predictions of anemias - Type and number of WBCs - diagnostic of various diseases Chemical analysis can provide a comprehensive picture of one's general health status in relation to normal values

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Lymphatic System: Overview

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Consists of two semi-independent parts: - A network of lymphatic vessels - Lymphoid tissues and organs scattered throughout the body, closely related to immune system Returns interstitial fluid and leaked plasma proteins back to the blood - Lymph - interstitial fluid once it has entered lymphatic vessels

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Lymphatic System

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Serves two main purposes - Get fluids that "leak" out of the blood back into the circulatory system. - Helps filter out "cooties" carried around in this fluid so the immune can act on them.

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Lymphatic Vessels

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One-way system, lymph flows toward the heart Lymph vessels include: - Microscopic, permeable, blind-ended capillaries - Lymphatic collecting vessels - Trunks and ducts

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Lymphatic Capillaries

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Similar to blood capillaries, with modifications: - Very permeable - Loosely joined endothelial minivalves - Withstand interstitial pressure and remain open The minivalves function as one-way gates that: - Allow interstitial fluid to enter lymph capillaries - Do not allow lymph to escape from the capillaries

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Lymphatic Capillaries

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During inflammation, lymph capillaries can absorb: - Cell debris - Pathogens - Cancer cells Cells in the lymph nodes cleanse and ;examine; this debris Lacteals - specialized lymph capillaries present in intestinal mucosa - Absorb digested fat and deliver chyle to the blood

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Lymphatic Collecting Vessels

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Have the same three tunics as veins Have thinner walls, with more internal valves Anastomose more frequently Collecting vessels in the skin travel with superficial veins Deep vessels travel with arteries Nutrients are supplied from branching vasa vasorum

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Lymphatic Trunks

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Lymphatic trunks are formed by the union of the largest collecting ducts Major trunks include: - Paired lumbar, bronchomediastinal, subclavian, and jugular trunks - A single intestinal trunk

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Lymphatic Trunks

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Lymph is delivered into one of two large trunks - Right lymphatic duct: drains the right upper arm and the right side of the head and thorax - Thoracic duct: arises from the cisterna chyli and drains the rest of the body

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Lymph Transport

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The lymphatic system lacks a pumping organ Vessels are low-pressure conduits Uses the same methods as veins to propel lymph: - Pulsations of nearby arteries - Contractions of smooth muscle in the walls of the lymphatics

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Lymphoid Cells

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Lymphocytes are the main cells involved in the immune response Two main varieties: - T cells - B cells

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Lymphocytes

answer

T cells and B cells protect the body against antigens Antigen: anything the body perceives as foreign - Bacteria and their toxins; viruses - Mismatched RBCs or cancer cells

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Lymphocytes

answer

T cells - Manage the immune response - Attack and destroy foreign cells B cells - Produce plasma cells, which secrete antibodies - Antibodies immobilize antigens

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Other Lymphoid Cells

answer

Macrophages: phagocytize foreign substances and help activate T cells Dendritic cells: spiny-looking cells with functions similar to macrophages Reticular cells: fibroblast-like cells that produce a stroma, or network, that supports other cell types in lymphoid organs

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Lymphoid Tissue

answer

Diffuse lymphatic tissue - scattered reticular tissue elements in every body organ - Larger collections appear in the lamina propria of mucous membranes and lymphoid organs Lymphatic follicles (nodules) - solid, spherical bodies consisting of tightly packed reticular elements and cells - Germinal center composed of dendritic and B cells - Found in isolation and as part of larger lymphoid organ:

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Lymph Nodes

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Principal lymphoid organs of the body Embedded in connective tissue and clustered along lymphatic vessels Aggregations of these nodes occur near the body surface in inguinal, axillary, and cervical regions of the body

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Lymph Nodes

answer

Two basic functions: - Filtration: macrophages destroy microorganisms and debris - Immune system activation: monitor for antigens and mount an attack against them

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Structure of a Lymph Node

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Nodes are bean shaped and surrounded by a fibrous capsule Trabeculae extended inward from the capsule and divide the node into compartments Nodes have two histologically distinct regions: a cortex and a medulla

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Structure of a Lymph Node

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Cortex contains follicles with germinal centers, heavy with dividing B cells Dendritic cells nearly encapsulate the follicles Deep cortex houses T cells in transit T cells circulate continuously among the blood, lymph nodes, and lymphatic stream

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Circulation in the Lymph Nodes

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Lymph enters via afferent lymphatic vessels It then enters a large subcapsular sinus and travels into smaller sinuses It meanders through these sinuses and exits the node at the hilus via efferent vessels Because there are fewer efferent vessels, lymph stagnates somewhat in the node This allows lymphocytes and macrophages time to carry out protective functions

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Other Lymphoid Organs

answer

The spleen, thymus gland, and tonsils Peyer's patches and bits of lymphatic tissue scattered in connective tissue All are composed of reticular connective tissue All help protect the body Only lymph nodes filter lymph

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Spleen

answer

Largest lymphoid organ, located on the left side of the abdominal cavity beneath the diaphragm It is served by the splenic artery and vein, which enter and exit at the hilus Functions: - Site of lymphocyte proliferation - Immune surveillance and response - Cleanses the blood

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Additional Spleen Functions

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Stores breakdown products of RBCs for later reuse - Spleen macrophages salvage and store iron for later use by bone marrow Site of fetal erythrocyte production (normally ceases after birth) Stores blood platelets

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Structure of the Spleen

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Surrounded by a fibrous capsule, it has trabeculae that extend inward and contains lymphocytes, macrophages, and huge numbers of erythrocytes Two distinct areas: - White pulp: containing mostly lymphocytes suspended on reticular fibers and involved in immune functions - Red pulp: remaining splenic tissue concerned with disposing of worn-out RBCs and bloodborne pathogens

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Thymus

answer

A bilobed organ that secretes hormones (thymosin and thymopoietin) that cause T lymphocytes to become immunocompetent Size of the thymus varies with age: - In infants, it is found in the inferior neck and extends into the mediastinum where it partially overlies the heart - It increases in size and is most active during childhood - It stops growing during adolescence and then gradually atrophies

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Internal Anatomy of the Thymus

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Thymic lobes contain an outer cortex and inner medulla Cortex contains densely packed lymphocytes and scattered macrophages Medulla contains fewer lymphocytes and thymic (Hassall's) corpuscles

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Thymus

answer

The thymus differs from other lymphoid organs in important ways - It functions strictly in T lymphocyte maturation - It does not directly fight antigens The stroma of the thymus consists of star-shaped epithelial cells (not reticular fibers) These thymocytes secrete the hormones that stimulate lymphocytes to become immunocompetent

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Tonsils

answer

Simplest lymphoid organs; form a ring of lymphatic tissue around the pharynx Location: - Palatine tonsils: either side of the posterior end of the oral cavity - Lingual tonsils: lie at the base of the tongue - Pharyngeal tonsil: posterior wall of the nasopharynx - Tubal tonsils: surround the openings of the auditory tubes into the pharynx

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Tonsils

answer

Lymphoid tissue of tonsils contains follicles with germinal centers Tonsil masses are not fully encapsulated Epithelial tissue overlying tonsil masses invaginates, forming blind-ended crypts Crypts trap and destroy bacteria and particulate matter

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Aggregates of Lymphoid Follicles

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Peyer's patches - isolated clusters of lymphoid tissue, similar to tonsils - Found in the wall of the distal portion of the small intestine - Similar structures are found in the appendix Peyer's patches and the appendix: - Destroy bacteria, preventing them from breaching the intestinal wall - Generate ;memory; lymphocytes for long-term immunity

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MALT

answer

MALT: mucosa-associated lymphatic tissue: - Peyer's patches, tonsils, and the appendix (digestive tract) - Lymphoid nodules in the walls of the bronchi (respiratory tract) MALT protects the digestive and respiratory systems from foreign matter

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