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143 Cards in this Set
- Front
- Back
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What is angiogenesis?
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The process of forming new blood cells
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Angiogenesis requires a balance of _______ and _______.
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Growth factors and inhibitory factors
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Angiogenesis can occur at most _____ cell layers away from blood supply.
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2
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How is angiogenesis promoted?
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Activator molecules can stimulate vascular endothelial cells to undergo mitosis and promote angiogenesis
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What are the two big activator or promoter molecules?
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VEGF - Vascular Endothelial Growth Factor
BFGF - Basic Fibroblast Growth Factor |
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The activator cells of angiogenesis stimulate ____ which leads to ______ which leads to proliferation of endothelial cells and differentiation of these cells into vascular tubes.
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NOs, NITRIC OXIDE
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Endothelial cells which proliferate in the vascular tubes due to NO secrete and synthesize a group of compounds called _____.
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MMP - metalloproteinases. These are enzymes that breakdown extracellular matrix which allows for migration of endothelial cells into tissue
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What are the big inhibitory factors?
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AAngiotensin - fragment of protein called plasminogin
Endotensin- fragment of collagen |
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What does angiotensin and endotensin do?
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both tells endothelial cells to self destruct by stimulating apoctosos
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What is the clinical significance of angiogenesis?
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Growth and Development, wound repair, menstrual cycle, tumor growth
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How is angiogenesis used to treat cancer?
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If you block angiogenesis you inhibit size of tumor
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What are two other inhibitor molecules other than angiotensin and endotensin?
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Interferons - released by WBC
Platelet factor 4 -> clotting system |
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How do drugs on the market inhibit cancer?
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Inhibit activation, inhibit signaling cascade, inhibit action of metalloproteinases
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What is wrong with the drugs developed to fight aggressive tumors by blocking VEGF ?
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This puts patients at risk for strokes
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What is blood composed of?
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Formed elements and plasma
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What is Total Blood Volume and what part of that is plasma?
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5.5 - 5.6 L of which 3-4 L is plasma
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What does plasma volume contribue to?
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Extracellular fluid compartment
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Describe composition of plasma portion of blood.
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91-93% water and 7-9% plasma proteins
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What is the major solute of plasma?
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Sodium
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What makes up the buffy coat between the plasma and the formed elements in blood?
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White Blood cells
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What makes up the formed elements of blood?
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Packed Red Blood Cells
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Where are plasma proteins made?
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Liver
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What are solutes in plasma?
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Ba+, Ca+, Cl-, HCO3
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What are the chemical messengers in plasma?
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FFA, AA, glucose
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What are the functions of blood?
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1. Carry oxygen bound iron in Hb
2. Acid- Base - protein binds H, Hb binds CO2-> leads to decrease in reaction that would produce O2; RBC's carbonic anhydrase allows us to carry bicarbonate in plasma 3. Hemostasis - transporting platelet clotting 4. Homeostasis - chemical messengers |
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What are the cells in the blood?
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Erythrocytes, Leukocytes, and Platelets
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What is hematocrit?
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It is the percent of blood occupied by erythrocytes
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What does hematocrit depend on?
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Age and sex
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Why do men have higher hematocrit than women?
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Because of higher testosterone and greater lean body mass. Women have loss of blood every month
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What is the approximate hematocrit for females and for males?
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females - 42% and males 45%
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What are the three types of plasma proteins?
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Plasma albumins, plasma globulins, and fibrinogen
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What does plasma albumin do and where is it made?
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Plasma albumin is produced by the liver and plays a major role in maintenance of osmotic pressures in blood in order to function as absorption force to pull water into capillary bed. Carrier protein binds to albumin as well.
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What happens with decreased albumin levels?
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Edema may result. This is a complication among liver and kidney disease
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What are the three types of plasma globulins? Where are the produced and what is their function?
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Alpha and beta globulins are produced by the liver nad play a key role in the transport of vitamins. Gamma globulins are produced by lymphocytes and function in immunity.
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Immunoglobins produced by Beta lmphocyte in plasma cells are _______ antibodies.
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Endogenous
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Where is fibrinogen produced and what is its function
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Liver, precursor for fibrin, and an important component for blood clotting system
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All blood cells is derived from where?
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Pluripotent hematopoietic stem cell in the bone marrow
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What are the two major lineages of blood cells from the stem cell in bone marrow?
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Myeloid and lymphoid
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What are hematopoietic Growth Factors?
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Collection of proteins that originate outside of the bone marrow. They promote growth of cells or stimulate differentiation of a specific cell type.
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What are some examples of hematopoietic growth factors?
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Interleukins are secreted by WBCs
Erythropoietin EPO increases RBC production Thrombopoietin makes more platelets |
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What are hte function of erythrocytes?
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Transport Hgb which binds and carries oxygen to peripheral tissues
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Hgb has binding sites for ____ and ___ in addition to oxygen.
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CO2 and H ions
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Hgb is a protein regulated by what mechanisms?
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Allosteric
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What is the Haldane effect?
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Binding of Oxygen to Hgb decreases its affinity to CO2 and vice versa
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How many chains is Hgb molecule composed of?
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4 Hgb chains
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Each Hgb chain contains a ______ and a _____.
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Heme moiety and globin portion
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Each heme portion on Hgb chain contains _____ and can carry _____ molecule of oxygen.
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Iron, 1
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So how many molecules of oxygen can a Hgb molecule carry?
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4 - 1 for each chain
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Why is the ability of Hgb to bind CO2 and H ions important?
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It is a body buffer
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How is bicarbonate allowed to be carried in blood?
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Enzyme Carbonic Anhydrase stimulates a reaction of H20 + CO2 -> H2CO3 -> H+ and HCO3-
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Sites for production of RBCs changes with what?
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The age of the individual
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Where are early life embryonic RBCs produced?
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Yolk sac, middle trimester produced in liver and late gestation to 5 years produced in bone marrow of all bones
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Where are RBCs produced from age 5-20?
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Many area of bone marrow are replaced with fatty substance so RBC produced by axial skeleton
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What do RBCs arise from?
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A cell CFU-E committed to erythrocyte lineage
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What is the first recognizable cell in erythrogenesis?
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Proerythroblast.
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Describe Erythrogenesis.
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Stem cell -> myeloid precursor -> erythroid precursor (CFU-E) -> Pro erythroblast -> this divides many times to form reticulocyte -> RBC
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Approximately ____% of RBCs circulating are reticulocytes.
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1
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When does final maturation of RBC occur?
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1-2 days in the circulation
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What is the shape of an RBC?
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Bioconcave disc that easily deforms as it passes through small capillary spaces. Large disc also provides large surface area for diffusion of gases
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What is lifespan of RBC?
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120 days
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What is happenign as RBC develops especially in series of different stages between proerythroblast and reticulocyte?
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Hgb increases, nucleus condenses, cell organelles disappear, concentration of Hgb in cell becomes 34%
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Why is exercise not allowed if hemoglobin is too low?
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Then you can't deliver enough oxygen and heart gets stressed
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What is the goal of RBC production?
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To equal the rate of RBC destruction
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What happens if there are too many RBCs in blood?
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This increases viscosity of blood and this impedes blood flow.
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What is the RBC number in males and females?
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Males - (4.7-6.1)(10^6)/ mm^3
Females - (4.2-5.4) (10^6)/mm^3 |
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If the number of RBCs is normal and Hgb/cell is normal what is the average value of Hgb for whole blood in males and females?
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16gm/dl for males and 14gm/dl for females
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What is the major regulator for RBC production?
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Erythropoietin hormone
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Where is Erythropoietin from?
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Synthesized and secreted by kidney
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When is secretion of erythropoietin stimulated?
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In response to low tissue oxygenation
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What happens to RBC in severe kidney disease?
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RBC production decliens and severe anemia occurs
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What are factors that cause enhanced secretion of erythropoietin?
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Anemia, altitude, hemorrhage, circulatory disease, cardiac failure, pulmonary disease
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When is an increase in RBC problematic?
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EPO abusers, blood doping, dehydration, burn victim, polycethemia vera (altitude)
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What has a profound effect on the quality of RBCs produced?
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Lack of essential nutritional elements causes maturation failure
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What are the metabolic requirements for RBC normal production?
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Iron from red meat, fortified foods, folate and B12 required by all cells for DNA
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Why is intrinsic B12 important?
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It protects stomach
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In situations of low oxgen, erythropoietin secretion reaches a maximum in about _____ hours. But it takes how long before increase in RBCs can be detected in blood?
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24, 5 days
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What is common cause of deficience of B12?
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Lack of intrinsic factor
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What does intrinsic factor do?
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It binds to B12 AND PREVENTS DIGESTION BY gi ENZYMES AND PROMOTES ABSORPTION INTO CIRCULATION
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Where is B12 Stored?
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Liver
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How long does it take for maturation failure to occur from b12 deficiency?
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3-4 years
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What nutritional requirement is necessary for normal sythesis of hemoglobin?
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Iron
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How much iron do males and females lose each day?
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Males - .6mg/day
Females - 1.3mg/day |
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What happens to RBCs during maturation failure when essential nutrients are lacking?
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RBCs produced are large and have irregular fragile membranes and shortened life span
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What is Anemia?
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Deficiency of total RBC's or amount of HgB per RBC. This causes a decrease in O2 that is delivered to body tissues
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What is a symptom of Anemia?
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Fatigue -> decrease tolerance to exercise
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Why does body require iron?
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To make normal healthy RBC and for normal synthesis of HgB
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Hemoglobin makes up _____% of RBC.
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35
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What is maturation failure?
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RBC did not mature properly possibly due to lack of iron
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What nutrients are important for RBC?
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Fe, B12, and folate
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When does Pernicious anemia occur?
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When there is no intrinsic factor to bind to B12 and protect it. Then you will not absorb enough B12
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What is Pica?
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People with anemia chew and eat non-food items such as ice
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In a case of anemia, how does kidney help?
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It detects the decrease in O2 and secretes EPO (Erythropoeitin)
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How are most daily requirements of iron met?
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Recycling iron from RBC destruction
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About _____% of total body iron is found in Hgb
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65
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How is iron stored in liver?
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As ferritin - iron bound to apoferritin
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What happens when ingested iron is absorbed into the circulation?
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It binds a protein called apotransferrin which is secreted by the liver and travels in circulation as transferrin. Transferrin binds with cell membrane in proerythroblast and is endocytosed and used to synthesize HgB
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Where is excess iron stored?
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In cells as hemosiderin which can be toxic to cells
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If 10% of ingested Fe is absorbed where does remainder go?
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It is in feces
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What happens when Fe enters epithelial cell?
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It is absorbed as free Fe or Fe binds to ferritin; feedback from periphery determines how much ferritin is made
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The ____ cells in gut play a key role in determining the amount of iron absorbed each day.
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GI
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While excess ingested iron is lost in the feces, continued ingestion of large amounts of iron causes what?
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Homosiderin deposition increase which is very toxic and liver cells are vulnerable to this
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Overall what are the steps of iron homeostasis in GI tract.
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Iron is ingested in GI tract and only 10% absorbed while rest lost in feces. GI epithelial tract controls how much Fe absorbed. Feedback regulates GI cell activity. Epithelial cell makes ferritin so when Fe enter GI epithelial cell there are two possibilities. Iron can be absorbed as free iron or can be bound to ferritin made by GI cell. Feedback from periphery determines how much ferrritin epithelial cells make.
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What is the response to iron homeostasis?
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Decrease mRNA for intestinal ferritin so less Fe bound to ferritin and more free to absorb
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How much iron your body absorbs depends on what and this depends on what?
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Feedback this dependends on amount of transferrin and liver
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What happens if we have decreased total body Iron?
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Want to decrease mRNA for intestinal ferritin and increase absorption
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What happens if we have increasing total body iron?
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Increased mRNA for intestinal ferritin and less absorbed
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Where is the major site of destruction for old fragile RBCs?
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Spleen
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What happens to old RBC when it goes through capillary?
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Its membrane will rupture because so fragile
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What is released when RBC membrane ruptures?
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Hgb (globin part) and Fe
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What happens to the Fe that is released when RBC membrane ruptures?
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It can go to liver for storage or it can go to bone marrow and recycled for HgB synthesis
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What happens to globin when released from RBC membrane rupture?
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It is acted on by macrophages which phagocytoze the globin and release a pigment called bilirubin.
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What does bilirubin do?
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It goes to liver and liver conjugates bilirubina and dumps it into bile since bilirubin is toxic
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What is jaundice?
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Sudden destruction of RBC, overwhelms livers ability to conjugate billirubin or happens prematurely
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Describe Type O blood.
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There are no antigens or cell surface markers this is the most common cell type. Universal donors
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Describe Type A blood.
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Has anti-B causing immune reaction against Type B or AB blood
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Describe Type AB blood.
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It has no anti agglutamines (antibodies) and is universal recipient. Only about 3% of population are AB
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How do anti-agglutinins develop after birth?
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The development of these antibodies develop in response to exposure of type A or type B blood through ingested food or bacteria
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What are some common symptoms of anemia?
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Dyspnea, Tachycardia, Palpitations, Decreased exercise tolerance
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What is Polycythemia Verea?
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Overproduction of RBC so must bloodlet
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Why will you make more RBC at altitude?
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Because decreased Oxygen stimulates kidneys to make EPO
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What are common causes of Polycythemia Vera?
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Altitude and cardiac failure
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What is hemostasis?
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Stoppage of bleeding. It involves interplay between blood vessels, thrombocytes or platelets, and clotting factors
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Describe the overall scheme of hemostasis?
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Injury to vessel causes vessel constriction which causes platelet aggregation and then coagulation
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During normal conditions which is more abundant anti-coagulants or pro-coagulants?
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Anti-coagulants
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Blood thinner mechanisms are _____.
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Anticoagulants
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What is hypercoaguble state?
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Elderly have tendency to clot, and post surgery. Elderly lose anticoagulatns with age
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What does doctor do when clot develops?
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He puts them on anticoagulant medication
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How can body sometimes naturally take care of clot?
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Fibrinolytic system naturally dissolves the clot
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What are some medications given as anticoagulates?
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Heparin and Coumadin
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What is platelet factor?
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It is cell surface marker that functions as cofactor and will stimulate platelet aggregation
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What does Thromboxane A2 do?
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It stimulates more platelet aggregation
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What stimulates the whole clotting cascade?
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Thrombin
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When platelets form platelet plug how do they adhere to collagen of skin?
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Through vWF - vonWILOFrans factor
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In clotting cascade we want blood to move from _____ to ____.
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Liquid to Gel or coagulated state
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How do we move blood from liquid to this coagulated state?
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Activate coagulating factor, which turns prothrombin into thrombin and this turns fibrinogen into fibrin.
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What is function of thrombin?
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Stimulates clotting cascade and needed to convert fibrinogen to fibrin. Thrombin activates Factor 13 which stabilizes fibrin and clot
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What is clotting factor I and II?
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Fibrin is I and Thrombin is II
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What is needed in the conversion of prothrombin to thrombin?
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Calcium
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Why is Vitamin K and Bile Salts needed for coagulation?
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Vitamin K is needed to produce prothrombin and clotting factors and bile salts are needed to absorb vitamin K
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What mechanisms limit extent of clot?
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Since we don't want clot all along the vessel, endothelial cells secrete 2 messengers (Nitric Oxide and Prostacyclin *PGI2) to inhibit Thromboxane A2 and inhibit platelet aggregation
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What is another inhibitor secreted by endothelial cells?
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antithrombin III inhibits thrombin and clotting factors It is activated when binds with heparin (which is on surface of endothelial cells). Also when thrombin binds with Thromobomodulin (endothelial cell receptor) this activates plasma protein C which inactivates some clotting factors
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What else can the endothelial cell do to limit extent of clot with Fibrinolytic system (dissolves clots after formed)?
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It takes plasminogen and converts it to plasmin which digests clot. This step is pushed by tPA
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What are some anticlotting drugs?
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Aspirin - blocks cyclooxygenase pathway
Drugs inhibiting vitamin K pathways Heparin TPA drugs blocking platelet function |
