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The Physiology of Blood:1/20. How much blood do we have? How do we describe blood and the RBCs found in it? How do we form blood and the hemoglobin that carries oxygen in the RBCs? How long do RBCs last in the circulation? What happens when RBCs undergo lysis? How do we form a hemostasis?
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The Physiology of Blood:1/20 • How much blood do we have? • How do we describe blood and the RBCs found in it? • How do we form blood and the hemoglobin that carries oxygen in the RBCs? • How long do RBCs last in the circulation? • What happens when RBCs undergo lysis? • How do we form a hemostasis? • How do we break up blood clots? • What are the drugs associated with manipulating the clotting process? • 5 point quiz on content of BLOOD LAB at the beginning of Monday’s lecture!! Read the lab cerefully prior to Monday.
Quiz: limited to CH 17Quiz at last 15 minutes at end of monday’s lecture Please include: First and Last name Name Only on side NAME Only ON TOP Watch eraser quality! Fill dots completely! Get new scantron if needed Written questions: ON BACK Extra Credit: ON BACK NAME AT TOP/FRONT for quick return in class monday
WHAT ARE THE BASIC FUNCTIONS OF BLOOD?WHY DO WE NEED IT? (DO WE NEED IT?) Partial List of Functions: #1: Oxygen/Carbon dioxide- #2: Nutrients/Wastes- #3: Hormones- #4: Protection- #5: Transport of Heat- Critical Concept: Without hemoglobin inside the erythrocyte, your blood cannot deliver enough oxygen to keep you alive! Oxygen has a LOW solubility in water by itself. What does blood look like: Oxygenated vs. Deoxygenate
HOW MUCH BLOOD DO YOU HAVE? Your body is mostly water and the blood represents about 8% of your body weight! (This will be a T.Q.) If a person weighed 220 lbs, how many liters of blood are there? If the person lost half their blood how much would you need to add to replace the lost blood? Memorize: 1,000 ml H20=1 liter=1 kg= 2.2 pounds Assume 1kg body wt. is about 1 liter of fluid How many kg is the person? (220 lbs)(1kg/2.2lb)=100kg How much blood does the person contain? (100 kg)(0.08)=8 kg 8kg of blood is about the same as 8 liters of blood! To replace the lost volume you would need 4 liters (half of what they started with). Try doing similar calculation for persons with different body weights on your own or in Supplemental Instruction. Folks have to do this all the time in an emergency room after major traumatic accidents.
How many erythrocytes do we have in our blood? About: 5 million/microliter5 billion/ml5 trillion/liter Typical Size is 2X7.5 micrometers/cell What happens to the RBC size in hypertonic or hypotonic environments? When would crenation or lysis occur? RBCs have donut-like shape to maximize their surface area and the rate of oxygen and carbon dioxide diffusion into/out of the cell. Shape? Take a balloon and squeeze two sides towards the center Are there any RBC Organelles? NO! RBCs are Anucleate: they can’t replace proteins if they become damaged. This limits their life-span to about 120 days and this is a huge problem! What does a erythrocyte RBC look like and what is so special about the shape?
What are the characteristics used to describe blood and the erythrocytes that contain the oxygen carrying hemoglobin? For lect/lab exam be able to interpret MCV, MCH, MCHC and MCD.
RBCs are produced in the red marrow of bone in response to hypoxia and EPO. RBCs live and deliver oxygen for about 120 days, but they get old, damaged and fragile. Fragile RBCs are destroyed by the spleen and liver. RBC parts are re-cycled to make new RBCs With the exception of heme which leaves the body in the urine or feces.
Hypoxia stimulates the formation of the endocrine hormone erythropoietin (EPO) by the kidney (also liver). EPO promotes erythropoiesis in the red marrow and ↑↑ O2 carrying capacity. How Does Erythropoiesis effect PCV and oxygen carrying capacity of the blood (why is hemoglobin required)? Hypoxia is- Anoxia is not- Anemia is- Polycythemia is not- What stimulates erythropoiesis? Why is EPO involved with: Olympic Athletes, High altitude, Emphysema, Smoking, Cancer treatment! Why do RBCs provide negative feedback to continue EPO secretion?
Excessive erythropoiesis (polycythemia) can be fatal! Why can’t welive permanently at an altitude of above about 17,000 feet? What would happen to your circulatory system if the PCV was 60%? Why is this a potential problem for athletes that abuse EPO? Why is EPO popular for athletes in the Tour De France?
Erythropoiesis requires making new hemoglobin. Iron is required for making functional hemoglobin. Iron can only be added to the system though intake in the diet. Often times people (vegetarians) have problems related to iron uptake from the gut and develop anemia. Only 10-35% of Fe++ is absorbed (ferrous iron is type found on hemes in meat) A meager 2-10% of dietary Fe+++ is absorbed (ferric iron type in most plants)
Volume produced/day: Why does Red Cross get a pint every 56 days? What are Old RBC/WBC Reserve Storage Sites: When do they become clinically significant? Normal RBC Disposal: Extra tiny 2-3 µM passages trap/test RBCs for viability in Spleen and Liver The good cells flex and pass through, while the old cells rupture (lysis) Macrophages and remnants create cellular waste: Biliverdin/bilirubin/bile Potentially toxic to neonates/adults! RBCs last about 120 days. What happens to RBCs at the end of their functional lifetimes?
How are the types of anemia clinically categorized? 1) Anemia from Inadequate Erythropoiesis: -Inability to make Hb- -Inability to make RBC- -Nutritional causes- -Hormonal cause (kidney damage)- -Cancer treatment- 2) Hemorrhagic Anemia: Blood Loss: Acute or Chronic 3) Hemolytic Anemia: A function of cellular “fragility” Cell Hemolysis -Sickle Cell Anemia -Rh Factor and erythroblastosis fetalis
There are Three Sequential Steps that lead to Hemostasis: Injury to a blood vessel creates a chain reactions that lead to hemostatis. Does blood need to leave the body when you bleed? (Think Bruises!) 1) Vascular Spasm/Vasoconstriction: Make Vessel Narrower Injury Pain and synaptic endings on smooth muscle Also: Epinephrine, Serotonin, Prostaglandins UltimatelySmooth Muscle Cells Contract and Vessel lumen Narrows 2) Platelet Plug Formation: Platelets adhere to the exposed collagen and to each other and begin massive degranulation! Degranulation/Exocytosis releases ADP, Serotonin, Thromboxane Positive feedback loop is initiated to make other platelets “stickier” to collagen and each other! Adherent platelets fill hole in vessel! 3) Coagulation or Clotting: Blood Clot Formation Last but MOST EFFECTIVE HEMOSTATIC METHOD Non-sticky fibrinogensticky fibrinTOUGH FIBRIN POLYMER “Clotting Cascade” describes the enzyme pathway leading to Polymer.
Prostacyclin and Nitric Oxide are produced by healthy endothelial cells and prevent platelet adhesion to vessel wall! No Clotting! Large Clot: “Thrombus”
Preventative Drugs: Aspirin: Coumadin: Warfarin: Hirudin: Problem Clots: Heart Attack Stroke Pulmonary Emboli Bruise Hematoma Coagulation is initiated by chemical signals that originate in the blood (intrinsic) or tissues (extrinsic). The lack of a factor could be fatal, and alternately inhibiting any step could save your life!
The inability to break up clots (fibrinolysis/thrombolysis) is fatal! Why is thrombolysis important if you experience a heart attack? How does one balance hemostasis and thrombolysis? This lets blood flow to your heart return after a temporary blockage by a clot. Hopefully blood flow returns before the infarct is too large!
How do we manipulate blood clotting clinically?Plasma: has clotting factors intact Serum: has clotting factors removed Factors Preventing Blood Clotting: collagen/tissue factor Invitro:EDTA vs. calcium, Sodium citrate vs. calcium Invivo drugs and enzymes: Coumadin vs. VitaminK Heparin vs. Thrombin Aspirin vs. Cyclooxygenase Genetics: Hemophilia Factor VIII: 1/5000 males, extremely rare in females AIDS risk in survivors of hemophilia Why are hematomas so common in persons taking anticoagulant medications? Why do they test clotting time so frequently? Factors Promoting Plasmin and Clot Lysis: Tissue plasminogen activator and Streptokinase Anticoagulation therapy and potential for bruising in elderly? Effects of diet: alcohol, garlic, grapes, cranberries?