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8/3/2019 Blood and Clotting Slides
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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 cellstransports oxygen and carbon dioxide
Leukocytes white blood cellsdefend body against pathogens
Platelets cell fragments formedfrom 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 percentageknown as the hematocrit)
_______________coat containsleukocytes and platelets (lessthan 1% of blood), the buffycoat is a thin, whitish layer
between the erythrocytes andplasma
Plasma rises to the top (55% ofblood)
Average blood volume Women = 5.0 L Men = 5.5 L
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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+,increaseblood viscosity, provide fuel during starvation
3 Major Classes of Plasma Proteins (synthesized in liver, except someglobulins synthesized by lymphocytes)
Albumins: Major contributor to plasma oncotic osmotic pressureand act as carriers
Globulins: Carriers, Clotting factors, Precursor proteins
(angiotensinogen), Immunoglobulins Fibrinogen:_______________
Nutrients: glucose, amino acids, lipids, vitaminsWastes: urea, bilirubin, creatinineGases (dissolved): oxygen, carbon dioxideHormonesElectrolytes
Relatively high concentrations of Na+ and Cl-
Relatively low concentrations of H+, HCO3-, K+, and Ca2+
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Ringers Solution
A solution of distilled water containing 8.6g sodium chloride, 0.3gpotassium chloride, and 0.33g calcium chloride per liter, the same
concentrations as their occurrence in body fluids.This solution is_______________to our blood and tissuesWhy?
Blood Plasma
Acidosis: blood becomes too acidicAlkalosis: blood becomes too basicIn each scenario, the respiratory system and kidneys help
restore blood pH to normal
Carbon dioxide can dissolve in water (blood plasma) andform_______________
CO2 + H2O H2CO3 (carbonic acid) H+ + HCO3- (bicarbonate)
Im an acid!
Cellular or Formed Elements
_______________: Red bloodcells (RBCs)
Leukocytes: White blood cells(WBCs)
Platelets (cell fragments)
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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 hemoglobinproduced after birth, fetal hemoglobin has a
gamma subunit in place of the beta subunit and
higher affinity for oxygen
Physiologic jaundice results when the livercannot 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 areawhich 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
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Hemoglobin in RBCs
Hb binds strongly (but reversibly) to oxygen98.5% oxygen bound to Hb and 1.5% dissolved
in plasmaEach hemoglobin molecule has four oxygen
binding sites
Globin + 4 heme groups = 4 polypeptides andHeme = iron-containing group
_______________-containing proteinCan also bind to CO2 and H+
Formation of Erythrocytes
Mature RBCs are unable to divide, grow, or synthesize proteinsWear out in 100 to 120 daysWhen worn out, RBCs are eliminated by phagocytes in the spleen or
liver
Lost cells are replaced by division of hemocytoblasts in the red bonemarrow
Iron is a component 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 oxygenlevels
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Control of Erythrocyte Production
Reduced O2
levels in blood
Stimulus: DecreasedRBC count, decreased
availability of O2 to
blood, or increased
tissue demands for O2Increased
O2- carrying
ability of blood
Kidney releases
erythropoietinEnhanced
erythropoiesis
Red bone
marrow
More
RBCs
Normal blood oxygen levels 100 mmHg
Imbalance
Imbalance
Erythropoietinstimulates
60 mmHg
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 shapedhemoglobin due to gene mutation on the Beta subunit of HB
_______________is an excessive or abnormal increase in thenumber of erythrocytes
Anemia: Decrease in the oxygen-carryingcapacity of blood
Dietary _______________ Iron: iron-deficiency anemia Pernicious: lack of Vitamin B12
Hemorrhagic anemia: bleedingHemolytic anemia
Malaria or Sickle cell anemiaAplastic anemia: bone marrow
defectRenal anemia: kidney disease
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Anemia
Leukocytes (white blood cells)
Leukocytes (white blood cells orWBCs)
Crucial in the bodys defenseagainst disease
These are complete cells, with anucleus and organelles
Able to move into and out of bloodvessels (diapedesis)
Can move by_______________motion
Can respond to chemicals releasedby damaged tissues (cytokines)
4,000 to 11,000 WBC per cubicmillimeter (microliter) of blood
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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)basophilsAgranulocytes Lack visible cytoplasmic granulesNuclei are spherical, oval,
or kidney-shaped
Include:1) _______________
2)monocytes
Abundance of Leukocytes
List of the WBCs from most toleast abundant
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
Easy way to rememberthis 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
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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
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Granulocyte: Basophils
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Lymphocytes: B Cells
B cells associated with antibodies2 major classes of B cells:
1)effector B cells become__________ cells and secrete
antibodies
2) memory B cells
B cell contacts antigen thenbecome a plasma cell
Plasma cell secretes antibodies(immunoglobulins)
Antibodies mark invaders fordestruction
Lymphocytes: T Cells
Helper T Cells secrete cytokines that enhance activity of B cells andother 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 bylysis
Memory T cells used for _______________ infectionSuppressor (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 cellscause lysis by secreting perforins
Can attack virus-infected cells withoutidentifying virus
Early defense against viral infections Cause lysisFast acting early immune response_______=major histocompatibility
complex
(a) Inhibitory NK cell receptors recognize self MHC class I and restrain NK cellactivation.
(b) When unimpeded by the inhibitory receptors, binding of NK cell activationreceptors 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 processNormal platelet count = 300,000/mm3(l)
Characteristics of Formed Elementsof the Blood
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Characteristics of Formed Elementsof the Blood
Hematopoiesis
Blood cell formation Occurs in red bone marrow All blood cells are derived from
a common stem cell
(________________)
Hemocytoblast differentiationLymphoid stem (lymphoblast)
cell produces lymphocytes
Myeloid stem (myeloblast) cellproduces all other formed
elements
Erythrocyte synthesisstimulated by erythropoietin
secreted from kidneys under
conditions of low oxygen levels
in blood flowing to kidneys
monocyte
Formation of White Blood Cells andPlatelets
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 abreak in a blood vessel
Hemostasis involves three phases1) __________________Vasoconstriction causes blood vessel to
spasm
Spasms narrow the blood vessel,decreasing blood loss
2) Platelet plug formation
Collagen fibers are exposed by a breakin a blood vessel a platelets become
sticky and cling to fibers
Anchored platelets release chemicalsto attract more platelets
Platelets pile up to form a platelet plug3) Coagulation (blood clotting)
Platelet Components
Platelet Plug needed forformation of a Blood Clot
____________Cell fragments
no nucleus has organelles & granules
100,000 500,000 / mL blood
Damagedtissue
Healthytissue
Preventing the Spread of Plug
Chemicals that prevent platelet aggregation: Prostacyclin (PGI2) - produced
in healthy endothelial cellsNitric oxide released by
healthy endothelial cells CD39 is an integral membraneprotein that keeps ADP levels
_______________
5 factors that activate a plateletplug are highlighted
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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 minutesThe clot remains as
endothelium regeneratesThe clot is broken down
after tissue repair
Intrinsic and Extrinsic CoagulationPathways
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)
Plasminogen
Plasmin
Dissolves Clot
Dissolving a Clot
Requires another cascade initiated by exposure of_______________
plasminogen activators
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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 criticalareas such as the brain
Role of Coagulation Factors in ClotFormation Disorders
_______________: a group of geneticdisorders caused by deficiency of gene
for specific coagulation factors
Von Willebrands disease: reducedlevels of vWf and decreases platelet
plug formation
Vitamin K deficiencies cause decreasedsynthesis of clotting factors
Thrombocytopenia Platelet deficiency Even normal movements can cause
bleeding from small blood vessels
that require platelets for clotting
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 quicklyTransfused 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 bodyrecognizes as foreign) may beattacked by the immune system
Antibodies are the recognizers thatattack foreign cells
Blood is typed by using antibodiesthat will cause blood with certain
proteins to clump (agglutination)
There are over 30 common red bloodcell antigens
The most vigorous transfusionreactions are caused by ABO and Rhblood group antigens
ABO Blood Groups
AB+
O-
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ABO Blood Groups
Blood type AB can receive A, B, AB, and Oblood, so AB+ is the universal recipient
Blood type B can receive Band O blood
Blood type A can receiveA and O blood
Blood type O can receive O blood, soO- 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 andanti B antibodies
Blood Typing
Blood samples are mixed with anti-Aand anti-B serum
Agglutination or no agglutinationleads to determining blood type
Typing for ABO and Rh factors isdone in the same manner
Cross matchingtesting foragglutination of donor RBCs by therecipients serum, and vice versa
Rh Blood Groups
Named because of the presence or absence of one of eightRh antigens (agglutinogen D) that was originally definedin 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 Rhmother carrying an Rh+ baby can causeproblems 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 thenewborn)
Danger occurs only when themother is Rhand the fatheris Rh+, and the child inheritsthe Rh+ factor
A_______________shot can preventbuildup of anti-Rh+ antibodiesin mothers blood