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What is blood?
A fluid connective tissue composed of:
- 1. plasma
- 2. Formed elements
- -Erythrocytes (RBCs)
- -Leukocytes (WBCs)
- -Platelets (cell fragments)
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Blood composition and physical characterisitics
Blood is a sticky, paque fluid tasting metallic and salty with the color scarlet (O 2 rich) to dark red (O 2 deficient)
pH--> 7.35-7.45 slightly alkaline
38 degrees C or 100.4 degrees F
About 8% of a person's body weight
- When spun in a centrifuge:
- -plasma is the least dese at 55% of the blood
- -Buffy coat in the middle makes up less than 1% (made of platelets and WBCs)
- -Hematocrit is the most dense at 45%
Hematocrit (RBCs) is 47% (plus or minus 5%) in males and 42% (plus or minus 5% in females)
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Functions of Blood
Blood: Distributes, protects, and regulates
Distributes: O2 and nutrients to body cells, metabolic wastes to the lungs (CO2) and kidneys (nitrogenous waste) for elimination
Protects Against: Blood loss (plasma protiens and platelets initiate clot formation), and Infection (antibodies, complement protiens, and WBCs defend against foreign invaders)
Regulates: body temperature by absorbing and distributing heat, normal pH using buffers (also the alkaline reserve in bicarbonate atoms), and adequate fluid volume in the circulatory system
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Blood Plasma
is 90% water, light yellow, and sticky
- 8% of the plasma is proteins and proteins are mostly produced by the liver
- *6-% albumin- major contributer to maintaing plasma osmotic pressure that helps keep water in the blood stream
- *36% globulins- gamma globulins are actually antibodies released by plasma cells
- *4% fibrinogen (threads to make fibrin for blood clot)
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Besides Proteins, Plasma also contains...
1. Nitrogenous by-products of metabolism- lactic acid, urea, and creatine
2. Nutrients- glucose, carbohydrates, amino acids
3. Electrolytes (help to maintain pH and plasma osmotic pressure)- Na+, K+, Ca2, Cl-, HCO3-
4. Respiratory Gases- O2 and CO2
5. Hormones
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Formed Elements in the blood
erythrocytes, leukocytes, and platelets
Only WBCs are complete cells
RBCs have no nuclei or organelles
Platelets are cell fragments
Most formed elements only survive in the blood stream for a few days
Most blood cells originate from red bone marrow and do not divide
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Erythrocytes
- Their structural characteristics contribute to gas transport
- -biconcave shape makes a huge surface area relative to volume
- -Over 97% Hb (not counting water)
- -No mitochondria; ATP production is anaerobic so none of the O2 it is carrying gets used up!
Perfect example of how function mirrors structure!
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Function of Erythrocytes
RBCs are dedicated to respiratory gas transport
Hb binds reversibly with O 2
- Hb structure: Protein globin- two alpha and two beta chains
- Heme pigmennt bonde to each globin chain contains iron
Iron atom in each heme can bind to one O 2 molecule
- Each Hb molecule can transport 4 O2
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Hemoglobin (Hb) loading and unloading
O2 loading in the lungs produces oxyhemoglobin (ruby red)
O2 unloading in the tissues produces deoxyhemoglobin or reduced hemoglobin (dark red)
CO2 loading in the tissues procuces carbaminohemoglobin (carries 20% CO2 in the blood)
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Hemotopoiesis (hemopoiesis)
Blood cell formation
Occurs in the red bone marrow of axial skeleton, gircles and proximal epiphyses of hermus and femur
- Hemocytoblasts (hemopoietic stem cells)-
- *give rise to all formed elements
- *hormones and frowth factos push the cell toward a specific pathway of blood cell development
New blood cells enter sinusoids
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Erythropoiesis
Red blood cell production
A hemocytoblast (myeloid stem cell) is transformed into a proerythroblast
proertythroblasts develop into early erythroblasts
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Phases of development in erythropoiesis
15 day process
- 1.Ribosome sythesis (Early to late erythroblast)
- 2. Hemoglobin accumulation (late to normoblast)
- 3. Ejection of the nucleus and formation of reticulocytes (normoblast to reticulocytes)
- Reticulocytes become mature erythrocytes (reticulocytes help determine the rate of RBC production)
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Regulation for Erythropoiesis
too few RBCs leads to hypoxia (O 2 deprivation)
too many RBCs increases blood viscosity
- balance between RBC production and desctruction depends on:
- 1. hormone controls
- 2. adequate supplies of iron, amino acids, annd B vitamins
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Hormonal Control of erythropoesis
- Erythropoietin (EPO)
- -direct stimulus for erythropoiesis
- -released by the kidneys (and a small amount in the liver) in response to hypoxia
- *hypoxia causes HIF (hypoxia-inducible factor) and as it accumulates it signals the release of EPO
- Effects of EPO
- - more rapid maturation of committed bone marrow cells
- -Increased curculatin reticulocyte count in 1-2 days
Testosterone also enhances Epo production, resulting in higher RBC counts in males
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What causes Hypoxia?
Hemorrhage or increased RBC destruction
Insufficient Hb (iron deficiency)
Reduced availability of O2 (such as high altitudes)
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Mechanism for regulation of Erythropoiesis
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Dietary requirements for Erythropoiesis
Nutrients: - amino acids, lipids, and carbohydrates
- Iron
- *stored in Hb (65%), the liver, spleen, and bone marrow
- *stored in cells as ferritin and hemosiderin because free iron is toxic
- *transported loosely bound to the protein transferrin
Vitamin B12 and folic acid- necessary for DNA synthesis for cell division
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Fate and destruction of Erythrocytes
Life span: 100-120 days
Old RBCs become fragile and Hb begins to degenerate
Macrophages engulf dying RBCs in the spleen (called the RBC graveyard)
- How it happens:
- 1. Heme and globin are separated
- 2. Iron is salvaged for reuse
- 3. Heme is degraded to yellow pigment bilirubin (binds to albumin for transport)
- 4. Liver secretes bilirubin (in bile) to intestines
- 5. Degraded pigment leaves body in the feces as tercobilin
- 6. Globin is metabolized into amino acids
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3 Main Causes of Anemia
1. Insufficient erythrocytes
2. Low Hb content
3. Abnormal Hb
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Causes of Anemia
Insufficient Erythrocytes
Hemorrhage anemia: acute or chronic loss of blood
Hemolytic anemia: RBCs rupture prematurely (due to mismatched transfusion, Hb abnonormalities, certain bacterial and parasitic infections)
Aplastic anemia: destruction or inhibition of red bone marrow (the cause is unknown in most cases
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Causes of Anemia
Low Hb content
- 1. Iron deficiency anemia
- - secondary result of hemorrhagic anemia or
- -inadequate intake of iron-containing foods or
- - impaired iron absorption (erythrocytes produced are microcytes, small and pale)
- 2. Pernicious Anemia
- -Deficiency of vitamin B12
- -Lack of intrinsic factor in stomache mucosa needed for absoption of B12
- -treated by intramuscular injection of B12 or application of nascobal (to the nasal lining once a week)
- *autoimmune and mostly effects the elderly
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Causes of Anemia
Abnormal Hemoglobin
- 1. Thalassemias (Sea blood)
- -absent or faulty globin chain
- -RBCs are thin, delicate, and Hb deficient
- 2. Sickle cell Anemia
- -defective gene codes for abnormal hemoglobin (HbS)
- -causes RBCs to become sickle shaped in low O2 situations
- *they then rupture easilty and block small blood vessels
- *strikes mostly african americans from the malaria belt b/c if someone only have one gene of SSA they have a better change against malaria
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Erythrocyte disorders
Polycythemia: excess of RBCs that increase blood viscosity making it thick and sludgy
- Results from:
- -Polycythemia vera: bone marrow cancer
- -Secondary polycythemia- when less O2 is available (high altitudes) or when EPO production increases
Treated by removing some blood and replacing it with saline
Blood doping: athletes remove some blood a few days before an event so that new RBCs are created, then the blood is put back in the day of the race. More RBCs means a high VO 2 max
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Leukocytes
make up less than 1% of total blood volume
can leave capillaries via diapededsis
move through tissue spaces by ameboid motion and positive chemotoxis (following a train of molecules released by damaged cells)
- Leukocytosis: when WBC count is over 11,000/mm3
- -normal response to bacterial or viral invasion
- -WBC count can double in just a few hours
- Two main types:
- granulocytes and agranulocytes
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Granulocytes
Neutrophils, eosinophils, and basophils
Cytoplasmic granules stain specifically with wright's stain
larger and shorter-lived than RBCs
Lobed nuclei
- Phagocytic- engulf foreign cells
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Neutrophils
most numerous WBCs
polymorphonuclear leukocytes (PMNs)
Fine granules take up bot acidic and basic dyes-gives the cytoplasm a lilac color
granules contain hydrolytic enzymes and defensins
Very Phagolytic-"bacteria slayers"-promoted by the respiratory burst where they stab bacteria
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Eosinophils
redstaining, bilobed nuclei
red to crimson (acidophilic) coarse, lysosome-like granules
digest parasitic worms that are too large to be phagocytized (they gather around a parasite and release enzymes to digest it)
modulators of the immmune response
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Basophils
rarest WBCs
- large, purplish-black (basophilic) granules contain histamine
- -histamine: an inflammatory checmical that acts as a vasodialiator (makes blood vessels dialate) and attracts other WBCs to the inflamed site
Are functionally similar to mast cells
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List the Leukocytes from most common to least common
Never Let Monkeys Eat Bananas
- Neutrophils
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils
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Agranulocytes
Lymphocytes and Monocytes
Lack visible cytoplasmic granules (they simply don't stain)
- have spherical or kidney shaped nuclei
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Lymphocytes
Large, dark purple, circular nuclei with a thin rim of blue cytoplasm
mostly in lymphoid tissue, few circulate in the blood
crucial to immunity
- Two types:
- T Cells- act against virus-infected cells and tumor cells
- B Cells- give rise to plasma cells, whic produce antibodies (immunoglobulins)
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Monocytes
The largest leukocytes
Abundant pale blue cytoplasm
Dark purple staining, U or kidney shaped nucleus, crushed glass looking cytoplasm
- They can leave circulation and enter tissues where they turn ameboid and differentiate into macrophages
- -actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections such as TB
Activate lymphocytes to mount an immune response
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Summarize the formed elements in the blood
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Leukopoiesis
Production of WBCs
- Stimulated by chemical messengers from bone marroe to mature WBCs
- -Interleukins (eg. IL-1, IL-2)
- -Colony-stimulation factors (CSFs)- named for the WBC type that they stimulate (ex. CSF granulocytes)
- All leukicytes originate from hemocytoblasts
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Leukocyte disorders
1.Leukopenia: abnormally low WBC count- drug induced (esp by anti-cancer agents)
- 2. Leukemias: cancerous conditions involving WBCs
- -Named according to the abnormal WBC clone involved
- -Myolocytic leukemia involved myeloblasts while lymphocytic leukemia involved lymphocytes
Acute leukemia involved blast-type cells and primarily affects children (quickly advancing)
Chronic leukemia is more prevalent in the elderly and is slow advancing
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Leukemia
bone marrow totally occupied with cancerous leukocytes
immature nonfunctional WBCs in the bloodstream
Death caused by internal hemorrhage and overwhelming infections
treatments include irradiation, antileukemic drugs, and stem cell transplants
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Platelets
Small fragments of Megakaryocytes (anucleate, degenerate quickly)
formation is regulated by thrombopoietin
blue staining outer region, purple granules
Granules contain serotonin, Ca2+, enzyme ADP, and platelet derived growth factor (PDGF)
They form a termporary platelet plug that helps seal breaks in blood vessels
Circulating platelets are kept inactive and mobile by Nitric Oxide (NO) and prostacyclin from endothelial cells of blood vessels
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Stages of Hemostasis
The fast series of reactions for stoppage of bleeding
- 1. Vascular Spasm
- 2. Platelet Plug Formation
- 3. Coagulation (blood clotting)
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Vascular spasm
Vasoconstriction of a damaged blood vessel
- Triggered by:
- -a direct injury
- -chemicals that are released by endothelial cells and platelets
- -pain reflexes
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Platelet plug formation
POSITIVE FEEDBACK MECHANISM
- at the site of blood vessel injury, platelets:
- -stick (aggregate) to exposed collagen fibers with the help of von Willebrand factor, a plasma protein
- -Swell, become spiked and sticky, and release chemical messengers
- *ADP causes more platelets to stick and release their contents
- *Serotonin and thromboxane A2 enhance vascular spasm and more platelet aggregation
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Coagulation
A set of reaction in which lood is transformed from a liquid to a gel using clotting factors and procoagulants
Reinforces the platelet plug with fibrin threads
- Three Phases of coagulation
- 1. Prothrombin activator is formed (both intrinsic and extrinsic pathways)
- 2. Prothrombin in converted into thrombin
- 3. Thrombin catalyzes the joing fibrinogen to form fibrin mesh
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