Blood (Week 8) Study Guide PDF

Study Guide Blood (Week 8) BLOOD LIFECYCLE A. State the sites where blood cells are produced and how this changes with age (including in the fetus) 1. Fetal – primarily liver 2. Infant – all bones 3. By mid 20’s i. Mostly ribs, vertebr...

Study Guide Blood (Week 8) BLOOD LIFECYCLE A. State the sites where blood cells are produced and how this changes with age (including in the fetus) 1. Fetal – primarily liver 2. Infant – all bones 3. By mid 20’s i. Mostly ribs, vertebrae, sternum ii. Also tibia and humerus iii. Dependent upon fatty deposits in bone marrow B. Describe the key stages of erythrocyte production / maturation 1. Pluripotent stem cell [nucleated] 2. Proerythroblast 3. [Various other erythroblast changes, becoming progressively less basophilic – don’t need to know the details] 4. Reticulocyte i. First time without a nucleus, but remnants of other material ii. Very few in the blood, since this stage is short-lived iii. More will be released in blood during acute anemia 5. Erythrocyte C. Briefly discuss the fate of erythrocytes in the blood 1. Live for ~120 days 2. Are metabolically active i. Various enzymes maintain (a) Cell membrane integrity (b) Hemoglobin integrity and iron (c) Transport of ions 3. Destroyed by macrophages i. Hemoglobin is phagocytized (a) Made into bilirubin ii. Iron released and carried back to bone marrow by transferrin 4. Self-destruction in the spleen i. Fragile erythrocytes are destroyed in passing through spleen’s trabeculae D. Describe the role of erythropoietin (EPO) in stimulating erythrocyte production 1. Low oxygenation sensed by the kidneys [and perhaps other tissues] 2. EPO is released within minutes to hours i. Proerythroblast production is increased ii. Rate of progression through each stage of erythrocyte development is more rapid Hematocrit E. State the approximate normal range for hematocrit 1. Females: Approximately 35-45 2. Males: Approximately 40-50 3. Overall: recognize it’s somewhere in that 35-50 range F. State what hematocrit measures 1. Percentage of red blood cells in the blood G. Briefly describe factors that influence hematocrit 1. Red blood cells i. Formation of blood cells (raises hematocrit) ii. Loss / destruction of blood cells (reduces hematocrit) 2. Plasma i. Hyperhydration (reduces hematocrit) ii. Dehydration (raises hematocrit) H. Briefly describe the effects of exercise training on hematocrit 1. Exercises training will i. Increase red blood cell production (increases hematocrit) (a) This increases TPR ii. Increase plasma volume (reduces hematocrit) (a) This reduces TPR 2. The ultimate result, whether hematocrit increases or decreases varies, but typically is a slight reduction in hematocrit i. Increase in plasma volume disproportionately greater than increase in red blood cells ii. Thus, adaptation is beneficial in two ways (a) Increased oxygen carrying capacity (more red blood cells), BUT… (b) Lower total peripheral resistance (easier for blood to flow) Hemoglobin I. Describe hemoglobin and its metabolism 1. Hemoglobin function i. Hemoglobin’s function is to bind oxygen molecules ii. LOTS of hemoglobin found on red blood cells 2. Hemoglobin structure i. 4 Heme Groups (a) Each has 1 iron ion (Fe2+) ii. Globin molecules 3. As old red blood cells are broken down by macrophages, hemoglobin is divided into three parts i. Globins (proteins) (a) These are recycled to form new hemoglobin ii. Heme group  (a) This is turned into bilirubin and eliminated (a) Macrophages convert heme into biliverdin (green color) (b) Bilvierdin is converted into unconjugated bilirubin (yellow color) (i) Unconjugated bilirubin is NOT water soluble (ii) Unconjugated bilirubin is transported to the liver (c) Unconjugated bilirubin is metabolized into conjugated bilirubin by the liver (i) Conjugated bilirubin is water soluble, so it can be easily eliminated (d) Conjugated bilirubin is then secreted into the bile, and into the small intestine (i) Conjugated bilirubin can be converted into stercobilin (brown color) 1. Eliminated in feces 2. Makes feces brown (ii) Conjugated bilirubin can be converted to urobilin and absorbed in the blood stream 1. Eliminated in urine 2. Contributes to urine’s yellow color iii. Iron from the heme group (a) This is recycled or stored J. Describe iron intake, metabolism, and storage 1. Iron intake and absorption from foods i. Fe2+ is FERROUS iron (a) Generally from animal products (b) Relatively easily absorbed in small intestine ii. Fe3+ is FERRIC iron (a) Generally from plant products (b) Must be converted to Fe2+ form before absorption 2. Iron goes through small intestine and into bloodstream i. Must be converted into Fe3+ (FERRIC) ii. Then binds to transferrin (a transport protein in blood) iii. Transferrin delivers iron to various tissues (a) Bone marrow – iron is used to make heme group (b) Liver – iron is stored (a) Ferritin – main storage protein (b) Hemosiderin – stores excess iron, beyond ferritin iv. When iron is needed (for times of heme generation), liver and other iron storage sites can release it from ferritin back into bloodstream (a) Controlled by the hormone hepcidin K. Describe jaundice 1. Yellowish/organish pigmentation of skin, eyes, and mucus membrane due to excess bilirun i. Known as Hyperbilirubinemia 2. Three categories of cause i. Pre-hepatic (before the liver) (a) Generally, due to red blood cell destruction (hemolysis) (b) Excess unconjugated bilirubin overwhelms the livers ability to process (conjugate) it (a) Since it cannot be conjugated quickly enough, it persists in the bloodstream  ii. Hepatic (a) The liver itself is not functioning correctly, so it cannot conjugate bilirubin (a) Since it cannot be conjugated, it persists in the bloodstream iii. Post-hepatic (after the liver) (a) The liver is able to conjugate bilirubin, but there is an obstruction which prevents it from being excreted (a) Examples include gall stone, tumors ANEMIA L. Briefly describe the main types of anemia 1. Blood loss anemia (hemorrhagic) i. Acute (a) Fluid is replaced in 1-3 days (b) Erythrocytes replaced in 3-6 weeks ii. Chronic (a) Insufficient iron replacement results in microcytic hypochromic anemia 2. Aplastic anemia i. Due to bone marrow dysfunction (a) Various causes , but cancer is a common one (a) From the cancer itself (b) From the treatments (radiation, chemotherapy, etc.) ii. Treated with blood transfusions or bone marrow transplants 3. Megaloblastic anemia i. Results from inappropriate maturation of erythroblasts (e.g. folic acid deficiency) ii. Most common forms are deficiency of Vitamin B12 and folic acid (folate, aka Vitamin B9) (a) Bone marrow cells are very rapidly growing cells (b) Require B12 and Folic acid for DNA synthesis (a) Insufficient amounts of these nutrients cause failure to nuclear maturation and division (b) Resulting red blood cells are fragile and have a decreased lifespan 4. Hemolytic anemia i. Destruction of erythrocytes faster than they can be replaced (a) Sickle cell anemia is one form of this (b) Depending on how fast this is happening, may cause jaundic 5. Dilutional anemia i. Red blood cells are diluted out by an increasing plasma volume (a) Happens during pregnancy M. Briefly describe the effects of anemia on cardiovascular function 1. Increased cardiac output (above the normal 5L/min) is necessary to maintain blood pressure 2. Increased cardiac output is sometimes necessary to maintain sufficient tissue oxygenation i. Dependent upon severity of anemia ii. Exacerbated during exercise, when oxygen demand is greatest Coagulation N. Discuss the process of thrombosis 1. Endothelial cell injury i. REMEMBER, this can be the typical type of injury that we would think of happening to a blood vessel, such as a laceration that causes bleeding… OR ii. It can also be associated with INFLAMMATION and ATHEROSCLEROSIS 2. Vasoconstriction occurs i. [Minor point - This cannot occur in capillaries, since they do not have smooth muscle] 3. Damage to the endothelium exposes the underlying extracellular matrix i. Platelets going by begin sticking to this ii. As they stick, they change shape and release cytokines which cause other platelets to stick to them iii. This is PRIMARY HEMOSTASIS (a) This is somewhat stable if left unperturbed, but can easily be disrupted 4. Tissue factor activates a cascade of events which cause i. MULTIPLE coagulation factors to become activated… (a) Abnormal function in any of these coagulation factors is responsible for various types of hemophilia (a) There are various degrees of hemophilia ranging from mild (e.g. easier bruising than normal) to severe (inability to stop bleeding from a minor impact) (b) Some of these are dependent on Vitamin K ii. That “coagulation cascade” ultimately activates THROMBIN iii. Thrombin ultimately causes fibrinogen to be turned into FIBRIN (a) Fibrin is the “glue” which holds together platelets. iv. This is SECONDARD HEMOSTASIS O. Discuss the process of fibrinolysis 1. After a thrombus (clot) is formed (explained above), at some point it must be broken down, and this is called fibrinolysis 2. Tissue Plasminogen Activator (tPA) is released from endothelium 3. tPA causes plasminogen to be turned into PLASMIN 4. Plasmin breaks down the previously formed fibrin i. Clot “dissolves” P. Briefly discuss the three key factors which can result in thrombosis 1. Abnormal blood flow i. Stasis (a) Example – Atrial fibrillation (b) Example – Bed rest (c) Example – Prolonged seated position (e.g., long flights, which can result in a DVT) ii. Turbulent blood flow (a) Example – atherosclerosis (b) Example – valvular and vascular stenosis 2. Endothelial injury (described above)  3. Hypercoagulability i. Inherited forms (e.g., the OPPOSITE of inherited hemophilia) ii. Acquired forms (e.g., from cancer or other chronic inflammation) Q. Appreciate that there is a constant balance between thrombosis and fibrinolysis which is constantly ongoing in our blood 1. In other words, tiny clots are constantly forming and being broken down R. Describe the clinical consequences of alterations in the balance between thrombosis and fibrinolysis 1. Excessive thrombosis OR insufficient fibrinolysis can increase the risk of ischemic disease i. Thromboembolisms in (a) Heart – Myocardial infarction (b) Brain – Stroke (c) Lungs – Pulmonary hypetension, arterial hypoxia (d) Kidneys – [we won’t go into detail, but they can disrupt normal kidney function, such as long term regulation of blood pressure, normal filtration, etc.] (e) Other organs – Ischemic consequences leading to dysfunction specific to that organ 2. Excessive fibrinolysis or insufficient thrombosis leads to abnormal bleeding i. Can be caused by too high of a dosage of anticoagulant therapy (a) Commonly prescribed following vascular procedures ii. Clinical signs (a) Easy bruising (b) Blood spots showing up on skin and mucus membranes (a) Petechia – small (b) Purpura – medium (c) Echymosis - large (c) Hematuria (urinating blood) (d) In more severe cases, hypovolemic shock (i.e., one essentially bleeds to death internally) S. Describe Deep Vein Thrombosis, including the clinical signs and risk factors 1. A clot in the veins, often the deeper veins in the legs i. It can occur elsewhere, including the arms ii. Usually only occurs in one limb at a time (a) So one of the clinical signs is asymmetric appearance 2. Clinical signs and symptoms include (typically unilateral): i. Signs: (a) Swelling (distal to site of clot) (b) Redness (erythema) ii. Symptoms: (a) Ache / pain in affected area (a) NOTE: This may be the reason why a patient presents to PT! (b) Shortness of breath (a) In part, due to reduced venous return to heart (b) Indicator of pieces of clot migrating to lungs (pulmonary emboli) 3. Risk factors i. Prolonged immobilization, especially in a gravity dependent position (a) Long-haul flights  (b) Long drives ii. Prothrombotic environment (a) Personal or family history of hypercoagulation disorders (b) Acute of chronic inflammation (a) Infectious disease (b) Chronic disease (c) Substantial muscle damage (c) Pregnancy (d) Trauma (e) Dehydration (f) Certain medication usage iii. Large veins 4. Management i. REFER TO EMERGENCY ROOM ii. DO NOT MOBILIZE, MASSAGE, EXERCISE, ETC!!!