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The Physiology of Blood: 1/23 and 1/25

The Physiology of Blood: 1/23 and 1/25. Chemical composition of plasma Lipoproteins: Good, Bad and Ugly Types of leukocytes What does hemoglobin look like? How does “cooperativity” ensure that hemoglobin is either 100% saturated with oxygen or 0% saturated?

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The Physiology of Blood: 1/23 and 1/25

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  1. The Physiology of Blood: 1/23 and 1/25 • Chemical composition of plasma • Lipoproteins: Good, Bad and Ugly • Types of leukocytes • What does hemoglobin look like? • How does “cooperativity” ensure that hemoglobin is either 100% saturated with oxygen or 0% saturated? • WHY is it important for a fetus to have Hb that are different from adult Hb? • How does oxygen binding by hemoglobin change during exercise? Why is this so beneficial? • What particles do we find in blood besides the “formed elements”? • Why are lipoproteins needed to move lipids in the blood? • Which lipoproteins are termed “Good” and “Bad”? • How are red blood cells typed with the ABO and Rh Systems? • What are the primary leukocytes and what is a differential blood count? • What is the specialized function of each type of WBC?

  2. What is the relative size of the materials in blood? Each erythrocytes contains about 380 million molecules of oxygen carrying hemoglobin (4 O2/Hb).

  3. PLASMA PROTEINS HAVE VARIED SIZES, WEIGHTS AND FUNCTIONS. WHILE THEY MAY NOT BE PRESENT IN LARGE AMOUNTS, THEY ARE CRITICAL FOR OUR HEALTH. Liver produces about 4 grams plasma protein/hour. …..But not the gamma globulins • Albumin: 60%- “Pickup truck of the human body” • Plasma Globulin Types 36%: -, -, and - • Fibrinogen 4%> Fibrin> Cross-linked Fibrin>Firm Clot Serum is plasma that has had the fibrinogen removed! • Plasma proteins influence drug availability- • What would happen to blood viscosity in a person who has chronic blood loss and anemia from a stomach ulcer and liver failure?

  4. WHAT HEALTH CONSEQUENCES COULD CHANGES IN PLASMA AND/OR BLOOD VISCOSITY HAVE TO A PERSON? • Plasma and blood viscosity relative to water- • PCV, disease and cardiac workload- Do “blood thinners” really change “viscosity”? What happens to plasma viscosity after a diuretic? • Osmotic pressure of the protein in the plasma creates an effect that pulls fluid from the interstitium into the plasma- -Kwashiorkor, Ascites, and dietary protein deficiency -What causes the pot-bellied appearance as child nears death? • Viscosity and clotting during severe dehydration: • Why does gangrene often occur in the limbs of a diabetic? • What happens to blood viscosity during severe frostbite? Why does gangrene often result?

  5. Lipoproteins and the similar Chylomicrons have an outer phospholipid layer with special proteins facing the water and variable lipid contents on the inside. These small particles help you move lipids between locations in the body.

  6. What particles carry fats in our bodies? Chylomicrons: largest and synthesized in the intestine. Carry_____________from the _______to the ________ Very Low Density Lipoproteins: VLDL: Big and synthesized by liver . Carry_______from the _______to the _________ Low Density Lipoproteins: LDL: VLDL-left over! Carry__________from the _______to the ______________ High Density Lipoproteins: HDL: smallest and synthesized by liver. Carry________from the _______to the ____________ WHY is HDL called “Good Cholesterol” and LDL “Bad Cholesterol” Plasma cholesterol and coronary heart disease/stroke risk: • Dietary influence and Genetic Influence: Why do we often die of a heart attack a few hours after a fatty Christmas dinner? Look and see next Wednesday!

  7. Can you predict the highest risk days for a thrombosis leading to a heart attack or stroke based on diet?Why do triglycerides potential increase the viscosity of the blood? Why can this lead to a thrombosis? My same blood after sitting for a couple days in the fridge. A: My blood before a greasy breakfast B: My TG rich Blood about 3 ½ hours after the greasy breakfast

  8. Chylomicrons carry triglycerides from gut to body VLDL generally carry triglycerides from liver to body (TG 3 Fatty Acids), VLDL becomes the LDL (bad) particles that deliver cholesterol to the body HDL (good) deliver peripheral cholesterol back to the liver High Plasma Triglycerides represent a health risk for atherosclerosis and a heart attack. The plasma or serum will look clear when low and milky when lipid levels are high. Plasma Triglycerides from low to high 90 mg/dL 130 mg/dL 450 mg/dL 1201 mg/dL

  9. Granulocytes: grainy cytoplasm Neutrophil: common (45-70%) Nucleus: sausages on a string! Phagocytic Count increased in presence to fight bacterial infections Eosinophil: uncommon (1-5%) Red/pink cytosol color Phagocytose Ab-Ag, makes defensive enzymes, allergies and inflammation Indicator of gut parasites Basophil: purple and rare(0.1-5%) Secrete histamine-dilator Secrete heparin-block clotting Intensify allergic response Agranulocytes: clear cytosol Lypmphocytes: common 20-40% Small cell with big round nucleus B-cell:makeAbs against Antigens T-cell and Nat. Killer Cell:Handle Ags Monocytes: (become macrophages) are slightly common 3-10% Clear cytosol/bean-like nucleus Become macrophages when mature Migrate in response to signals Don’t Forget RBC: no nucleus: for gas transport MOST COMMON Platelet: Cellular fragments that mediate hemostasis What to know about the five white blood cell (leukocyte) types? 1) ID by appearance, 2) ID by function, 3) Relative frequency

  10. Leukemia: WBC Cancer Myeloid Cancer: granulocytes Lymphoid Cancer: agranulocytes Chemotherapy often results in a fatal opportunist infection in patient! Because no replacement WBCs are available when infection is encountered. Leukopenia: “low WBC numbers: under 5,000/ul” Leukocytosis: “high WBC numbers: +10,000/ul”Differential Counts: # of each WBC as % of total WBC countHematopoeisis: make new RBCs Leukopoiesis: make new WBCs

  11. Hematocrit (Hct%) or Packed Cell Volume (PCV) Blood is composed of fluids (plasma/serum) and formed elements (erythrocytes, leukocytes and platelets) Percent (%) of blood volume filled with erythrocytes is called Hematocrit (Hct%) sometimes refered to as PCV or Packed Cell Volume Average for male: 47% Average for female: 42% Calculations: Total tube volume 100 ml, with 25 ml formed elements and 75ml plasma: Hct=25% -”Anemic” Total tube length 50mm, 20 mm formed elements (30mm plasma):Hct=40% -”Normal” Total tube volume 60 ml, with 40 ml formed elements and 20ml plasma: Hct=60% -”Excess RBCs”

  12. Hemoglobin consists of 4 protein subunits (globins) and each globin has a heme at its center. Each heme holds a single Fe++ and can hold a single O2 molecule (4 O2 /hemoglobin).There are about 380,000,000 hemoglobins in each erythrocyte!Each erythrocyte can carry up to about 4X380,000,000 oxygens!

  13. Hemoglobin has 4 globins, 4 hemes, 4 Fe++, and binds up to a maximum of 4 O2 (or No O2 at all) The protein subunits are called “globins” Two can be “alpha” in adult or fetus Two can be “beta” in adult-appear just before birth Two can be “gamma” in fetus-lost right around birth The “HEME” is a ring like structure that has Fe++ in the center. Oxygen is attracted to the Fe++ that binds it temporarily and releases it later where needed. Attachment and release is determined by concentration gradients (What are gradients in LUNG or HEART?) Oxygen tends to fall of the heme if there is little oxygen around the heme….so oxygen is then supplied to tissues. Oxygen binds to the heme when there is plenty of oxygen available and none is attached to the heme…this condition occurs when erythrocytes are in the capillaries that line the alveoli of the lung.

  14. 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. Items in red good for one question on the lecture test. Match formula to name/meaning.

  15. Content for Lecture Test #1 Stops here50 points: 46 multiple choice questions + 4 written pts + 2 pt extra credit The rest of this material will be on test #2Don’t Forget 5 point Monday lab-prequiz too!“Let the notes be your guide to what is most important and most likely to appear on the exam”….but ya cannot do it without reading the book and comparing notes to book.Look at questions in back of chapterLook at practice quiz questionsCreate your own study guide an exam questions from your notesPractice test is ONLY to help you understand test format….it is NOT a “study guide”.Bring a CLEAN scantron (50 que/ half sheet)….Write written questions anywhere you want ON BACK OF SCANTONDouble check your bubble answers for smears, mistakes, etc. What you hand in is what is graded, instructor will not correct for poorly erased, partially filled bubbles, or other errors.

  16. “Cooperativity” describes how the four globins of hemoglobin interact with each other and oxygen. When all 4 hemes are without oxygen (empty) affinity is low, but gradient is high. The binding of oxygen to any one heme affects the remaining three and makes them more likely to bind oxygen. When another oxygen binds, it makes the remaining two even more likely to bind oxygen. Binding of a third oxygen tremendously increases the affinity of the last empty heme to find and oxygen. Assuming an oxygen can bind the heme, the hemoglobin is now filled (100% saturated) with oxygen. INVERSE: When any single heme in the hemoglobin looses an oxygen, the other three are more likely to lose an oxygen, etc… Net Result? Hemes want to be completely filled with oxygen or completely empty! This gives the binding curve a “sigmoid” shape. This is HUGELY important physiologically!

  17. Myoglobin in muscle has one heme and globin (No Cooperativity).Hemoglobin in a erythrocyte has four hemes and globins.Why do the oxygen binding characteristics of these two proteins look so different? Hyperbolic vs. Sigmoid Curve Oxygen is bound to almost 100% of available Hb-hemes in the lung. 1) Oxygen is removed from the hemoglobin 2) Percent saturation reduced (oxygen used). Hb has “Cooperativity”--------- Mb has NO “Cooperativity”!

  18. Why would you want fetal hemoglobin (2 gamma subunits) to bind oxygen much more tightly than adult hemoglobin? Is there more oxygen in the blood of the fetus or the mother? Like all molecules oxygen can only diffuse down concentration gradients in the body. DANGER! Carbon monoxide has an extremely high affinity for Hb (Hb-CO), so oxygen cannot bind Hb in the lung!

  19. The Bohr Effect is amazing! Acids accumulate ( ↓pH) in metabolically active tissues! This is a signal that oxygen needs have increased in the tissue! If oxygen needs increase, oxygen delivery needs to increase! HOW IS THIS DONE? Protons (H+ or acids) are a signal that cause the hemoglobins to DUMP their oxygen in acidic tissues that should also be hypoxic! The Bohr Effect says that as conditions become more acidic (even slightly) the hemoglobin is more likely to release its oxygen. The reverse can also occur…..remember hyperventilating as a kid? This causes your blood pH to become alkaline and you pass out because you have plent of oxygen in the blood, you cannot remove the oxygen from your hemoglobin properly in your brain!

  20. The shift in the oxygen binding curve to the right means less oxygen will be attached to the hemoglobins in acidic conditions! (high O2use) So oxygen leaves hemoglobin and is delivered to where it is needed most! ↑Carbon dioxide and ↑Temperature have similar effects.

  21. If the Hb is not bound by oxygen you will appear cyanotic (bluish)! Remember that only a tiny amount of oxygen can dissolve directly in blood! (see bottom yellow line) The more hemoglobin you have in your blood, the more oxygen your blood can deliver (that simple)!If the tissues are warmer or more acidic, the oxygen is more likely to leave the hemoglobin so it can be used in this tissue (that simple). Shift occurs if pH↓ or Temp. ↑

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