Blood

Blood
The only fluid tissue in the human body Classified as a connective tissue Components of blood 1) Living cells called _______________ Erythrocytes red blood cells transports oxygen and carbon dioxide Leukocytes white blood cells defend body against pathogens Platelets cell fragments formed from megakaryocytes, important in blood clotting 2) Non-living matrix: plasma is the fluid and solutes

Blood Hematocrit and Beyond

When blood is centrifuged Erythrocytes sink to the bottom (45% of blood, a percentage known as the hematocrit) _______________coat contains leukocytes and platelets (less than 1% of blood), the buffy coat is a thin, whitish layer between the erythrocytes and plasma Plasma rises to the top (55% of blood) Average blood volume Women = 5.0 L Men = 5.5 L

kwashiorkor

Physical Characteristics of Blood

Blood is used as a vehicle of transport Color range Oxygen-rich blood is scarlet red Oxygen-poor blood is dull red pH between 7.357.45 (7.4) Blood temperature is slightly higher than body temperature at 38 (_______________) Blood makes up 8% of body weight

Blood Plasma is ~90% Water

6-8% proteins which: increase osmotic pressure, buffer H+, increase blood viscosity, provide fuel during starvation 3 Major Classes of Plasma Proteins (synthesized in liver, except some globulins synthesized by lymphocytes) Albumins: Major contributor to plasma oncotic osmotic pressure and act as carriers Globulins: Carriers, Clotting factors, Precursor proteins (angiotensinogen), Immunoglobulins Fibrinogen: _______________ Nutrients: glucose, amino acids, lipids, vitamins Wastes: urea, bilirubin, creatinine Gases (dissolved): oxygen, carbon dioxide Hormones Electrolytes Relatively high concentrations of Na+ and ClRelatively low concentrations of H+, HCO3-, K+, and Ca2+

Ringers Solution
A solution of distilled water containing 8.6g sodium chloride, 0.3g potassium chloride, and 0.33g calcium chloride per liter, the same concentrations as their occurrence in body fluids. This solution is _______________to our blood and tissues Why?

Blood Plasma
Acidosis: blood becomes too acidic Alkalosis: blood becomes too basic In each scenario, the respiratory system and kidneys help restore blood pH to normal Carbon dioxide can dissolve in water (blood plasma) and form _______________ CO2 + H2O H2CO3 (carbonic acid) H+ + HCO3- (bicarbonate)

Im an acid!

Cellular or Formed Elements

_______________: Red blood cells (RBCs) Leukocytes: White blood cells (WBCs) Platelets (cell fragments)

Developmental Aspects of Blood Cells

Sites of blood cell formation The fetal liver and spleen are early sites of blood cell formation Bone marrow takes over _______________ by the seventh month Fetal hemoglobin differs from hemoglobin produced after birth, fetal hemoglobin has a gamma subunit in place of the beta subunit and higher affinity for oxygen Physiologic jaundice results when the liver cannot rid the body of hemoglobin breakdown products fast enough

Erythrocytes
Erythrocytes (red blood cells or RBCs) Main function is to carry oxygen Anatomy of circulating erythrocytes biconcave disk: large surface area which favors diffusion Essentially bags of hemoglobin Anucleate (no nucleus) Contain very few organelles No _______________ Use anaerobic glycolysis 5-6 billion RBCs per ml of blood Flexible membrane Also function to maintain osmolarity and blood/plasma pH

Hemoglobin in RBCs
Hb binds strongly (but reversibly) to oxygen 98.5% oxygen bound to Hb and 1.5% dissolved in plasma Each hemoglobin molecule has four oxygen binding sites Globin + 4 heme groups = 4 polypeptides and Heme = iron-containing group _______________-containing protein Can also bind to CO2 and H+

Formation of Erythrocytes
Mature RBCs are unable to divide, grow, or synthesize proteins Wear out in 100 to 120 days When worn out, RBCs are eliminated by phagocytes in the spleen or liver Lost cells are replaced by division of hemocytoblasts in the red bone marrow Iron is a comp onent of_______________ Normal hemoglobin content of blood Men: 13 18 gram /dL Women: 12 16 gram /dL

Control of Erythrocyte Production

Rate is controlled by a hormone (_______________) Kidneys produce most erythropoietin as a response to reduced oxygen levels in the blood Homeostasis is maintained by negative feedback from blood oxygen levels

Control of Erythrocyte Production

Im bal anc e Im

Normal blood oxygen levels 100 mmHg

bal anc e

Increased O2- carrying ability of blood

60 mmHg

Stimulus: Decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2 Reduced O2 levels in blood

More RBCs Enhanced erythropoiesis Red bone marrow

Erythropoietin stimulates

Kidney releases erythropoietin

Hemoglobin in RBCs
Homeostatic imbalance of RBCs Anemia is a decrease in the oxygen-carrying ability of the blood Sickle cell anemia (SCA) results from abnormally shaped hemoglobin due to gene mutation on the Beta subunit of HB _______________ is an excessive or abnormal increase in the number of erythrocytes

Anemia: Decrease in the oxygen-carrying capacity of blood

Dietary _______________ Iron: iron-deficiency anemia Pernicious: lack of Vitamin B12 Hemorrhagic anemia: bleeding Hemolytic anemia Malaria or Sickle cell anemia Aplastic anemia: bone marrow defect Renal anemia: kidney disease

Anemia

Leukocytes (white blood cells)

Leukocytes (white blood cells or WBCs) Crucial in the bodys defense against disease These are complete cells, with a nucleus and organelles Able to move into and out of blood vessels (diapedesis) Can move by _______________ motion Can respond to chemicals released by damaged tissues (cytokines) 4,000 to 11,000 WBC per cubic millimeter (microliter) of blood

Types of Leukocytes
Two Major Classes of Leukocytes Granulocytes Granules in their cytoplasm can be stained Possess lobed nuclei Include 1)neutrophils, 2)eosinophils, and 3)basophils Agranulocytes Lack visible cytoplasmic granules Nuclei are spherical, oval, or kidney-shaped Include: 1) _______________ 2)monocytes

Abundance of Leukocytes
List of the WBCs from most to least abundant Neutrophils Lymphocytes Monocytes Eosinophils Basophils Easy way to remember this list Never Let Monkeys Eat Bananas

Leukocytes: Granulocytes
Types of granulocytes _______________Multilobed nucleus with fine granules Act as phagocytes at active sites of infection Eosinophils Large brick-red cytoplasmic granules Found in response to allergies and parasitic worms Basophils Have histamine-containing granules Initiate inflammation

Leukocytes: Agranulocytes
Types of agranulocytes _____________________ Nucleus fills most of the cell Play an important role in the immune response Monocytes Largest of the white blood cells Function as macrophages Important in fighting chronic infection

Granulocyte: Neutrophils
40-70% of leukocytes in blood Phagocyte Secretes _________________ Circulate in blood 7-10 hours Migrate to tissues for a few days Increase in number during infections

Granulocyte: Eosinophils
1-4% of __________________ Phagocytes (but not main mechanism of action) Defend against parasitic invaders (e.g. worms) Granules contain toxic molecules that attack parasites

Granulocyte: Basophils
<1% of leukocytes Non-phagocytic May defend against large parasites by releasing toxic substances Contribute to allergic reactions _____________ Heparin

Agranulocytes: Monocytes become Macrophages

4-8% of leukocytes _________________ New monocytes circulate in blood for a few hours then Migrate to tissues macrophages Wandering macrophages Fixed macrophages

Agranulocytes: Lymphocytes
20-45% of WBCs 3 types of Lymphocytes B lymphocytes (B cells) T lymphocytes (T cells) ________ cells (also called natural killer or NK cells)

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Lymphocytes: B Cells
B cells associated with antibodies 2 major classes of B cells: 1)effector B cells become __________ cells and secrete antibodies 2) memory B cells B cell contacts antigen then become a plasma cell Plasma cell secretes antibodies (immunoglobulins) Antibodies mark invaders for destruction

Lymphocytes: T Cells
Helper T Cells secrete cytokines that enhance activity of B cells and other T cells enhances activity of macrophages and NK cells Cytotoxic T Cells kill virus-infected cells, abnormal cells, and bacteria, Secretory products form pores in target cell membrane, Kills cells by lysis Memory T cells used for _______________ infection Suppressor (regulatory) T Cells secrete cytokines that suppress activity of B cells and other T cells and used to end an immune response

Lymphocytes: Natural Killer Cells (Null Cells)

Recognize abnormal or infected cells cause lysis by secreting perforins Can attack virus-infected cells without identifying virus Early defense against viral infections Cause lysis Fast acting early immune response

_______=major histocompatibility complex

(a) Inhibitory NK cell receptors recognize self MHC class I and restrain NK cell activation. (b) When unimpeded by the inhibitory receptors, binding of NK cell activation receptors to their ligands on target cells results in NK cell stimulation.

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Leukocyte Issues
Abnormal numbers of leukocytes ____________________ WBC count above 11,000 leukocytes/mm3 Generally indicates an infection Leukopenia Abnormally low leukocyte level Commonly caused by certain drugs such as corticosteroids and anticancer agents Leukemia occurs when bone marrow becomes cancerous, turns out excess WBC

Platelets
Platelets (a.k.a. thrombocytes) Derived from ruptured multinucleate cells (_____________________) Needed for the clotting process 3 Normal platelet count = 300,000/mm (l)

Characteristics of Formed Elements of the Blood

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Characteristics of Formed Elements of the Blood

Hematopoiesis
Blood cell formation Occurs in red bone marrow All blood cells are derived from a common stem cell (________________) Hemocytoblast differentiation Lymphoid stem (lymphoblast) cell produces lymphocytes Myeloid stem (myeloblast) cell produces all other formed elements Erythrocyte synthesis stimulated by erythropoietin secreted from kidneys under conditions of low oxygen levels in blood flowing to kidneys

monocyte

Formation of White Blood Cells and Platelets

Controlled by _____________ Colony stimulating factors (CSFs) and interleukins prompt bone marrow to generate leukocytes Thrombopoietin stimulates production of platelets

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Hemostasis
Stoppage of bleeding resulting from a break in a blood vessel Hemostasis involves three phases 1) __________________ Vasoconstriction causes blood vessel to spasm Spasms narrow the blood vessel, decreasing blood loss 2) Platelet plug formation Collagen fibers are exposed by a break in a blood vessel a platelets become sticky and cling to fibers Anchored platelets release chemicals to attract more platelets Platelets pile up to form a platelet plug 3) Coagulation (blood clotting)

Platelet Components
Platelet Plug needed for formation of a Blood Clot ____________ Cell fragments no nucleus has organelles & granules 100,000 500,000 / mL blood

Preventing the Spread of Plug

Chemicals that prevent platelet aggregation: Prostacyclin (PGI2) - produced in healthy endothelial cells Nitric oxide released by healthy endothelial cells CD39 is an integral membrane protein that keeps ADP levels _______________
5 factors that activate a platelet plug are highlighted

Damaged tissue

Healthy tissue

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Aspirin
Prevents platelet _______________ Inhibits the activation of thromboxane A2

Hemostasis
_______________ Injured tissues release tissue factor (TF) PF3 (a phospholipid) interacts with TF, blood protein clotting factors, and calcium ions to trigger a clotting cascade Prothrombin activator converts prothrombin to thrombin (an enzyme) Thrombin joins fibrinogen proteins into hair-like molecules of insoluble fibrin Fibrin forms a meshwork (the basis for a clot) Blood usually clots within 3 to 6 minutes The clot remains as endothelium regenerates The clot is broken down after tissue repair

Intrinsic and Extrinsic Coagulation Pathways

Intrinsic Pathway trigger = exposed collagen

Extrinsic Pathway Requires Tissue Factor III

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Role of Thrombin in Blood Clotting

Clot Formation
Fibrinogen _______________ (mesh) (Fibrin clot = blood clot)

Dissolving a Clot
Requires another cascade initiated by exposure of _______________
Plasminogen plasminogen activators Plasmin

Dissolves Clot

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Undesirable Clotting
Thrombus A clot in an unbroken blood vessel Can be deadly in areas like the heart _______________ A thrombus that breaks away and floats freely in the bloodstream Can later clog vessels in critical areas such as the brain

_______________: a group of genetic disorders caused by deficiency of gene for specific coagulation factors Von Willebrands disease: reduced levels of vWf and decreases platelet plug formation Vitamin K deficiencies cause decreased synthesis of clotting factors Thrombocytopenia Platelet deficiency Even normal movements can cause bleeding from small blood vessels that require platelets for clotting

Role of Coagulation Factors in Clot Formation Disorders

Blood Groups and Transfusions

Large losses of blood have serious consequences Loss of 1530% causes _______________ Loss of over 30% causes shock, which can be fatal Transfusions are the only way to replace blood quickly Transfused blood must be of the same or compatible blood group(s)

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Human Blood Groups

Blood contains _______________ determined proteins Antigens (a substance the body recognizes as foreign) may be attacked by the immune system Antibodies are the recognizers that attack foreign cells Blood is typed by using antibodies that will cause blood with certain proteins to clump (agglutination) There are over 30 common red blood cell antigens The most vigorous transfusion reactions are caused by ABO and Rh blood group antigens

ABO Blood Groups

AB+

O-

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ABO Blood Groups

Blood type AB can receive A, B, AB, and O blood, so AB+ is the universal recipient Blood type B can receive B and O blood Blood type A can receive A and O blood Blood type O can receive O blood, so O- is the universal donor Blood types: _______________ Due to antigens on surface of RBCs Type A A antigens, anti-B antibodies Type B B antigens, anti-A antibodies Type AB A and B antigens, no A or B antibodies Type O no modified antigens, anti-A and anti B antibodies

Blood Typing
Blood samples are mixed with anti-A and anti-B serum Agglutination or no agglutination leads to determining blood type Typing for ABO and Rh factors is done in the same manner Cross matchingtesting for agglutination of donor RBCs by the recipients serum, and vice versa

Rh Blood Groups
Named because of the presence or absence of one of eight Rh antigens (agglutinogen D) that was originally defined in Rhesus monkeys Most Americans are Rh+ (Rh positive) Problems can occur in mixing Rh+ blood into a body with Rh (_______________) blood

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Rh Dangers During Pregnancy: Erythroblastosis fetalis, Rhesus disease

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 mothers immune system produces antibodies to attack the Rh+ blood (hemolytic disease of the newborn) Danger occurs only when the mother is Rh and the father is Rh+, and the child inherits the Rh+ factor A _______________shot can prevent buildup of anti-Rh+ antibodies in mothers blood

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