WEEK+12+Hematologic

__//**4. Discuss the structure and function of the cellular components of blood, the spleen and the lymph nodes.(Lewis, 666-668) (Heuther, 482-486-TABLE 19-2)**//__

**RBC's(4.2-6.2):** Transport of O2 and Co2(tissue oxygenation) & acid base balance, because Hemoglobin is a buffer
__Bi-concave shape__: provides surface area/volume ratio that is perfect for carrying gases in & out of cells __Reversibly deformability__: allow RBC to alter shape(torpedo like) to squeeze through microciculation

**WBC's**(5-10,000): Originate in bone marrow
__Granulocytes__-**MATURE IN THE MARROW LIVE FOR HRS TO DAYS** primary fucktion is PHAGOCYTOSIS, contain enzymes for killing microbes and catabolizing debris, contain biochemical mediators. __Agranulotcytes-__ **MATURE IN BLOOD OR OTHER LOCATIONS** Immune & inflammatory response, powerful phagocytes, ingest dead cell (RBC's) and debris
 * Neutrophils (55-70%)-early inflammation acute bacterial infection Mature=segs; immature=bands
 * Eosiniphils (1-6%)- allergies and parasites, IgE
 * basophils (1%) release heparin(Anticoagulent for clot lysis), serotonin & histamine. Also part of allergy.
 * Monocytes (5%) - present in blood for 3 days then migrate into tissue to become Macrophages, can live for years, can cell divide
 * Lymphocytes (25-36%)- primary cells of immune response, live for years

====**Platelets**:(140-340,000) essential for blood clots and control bleeding, release biochemical mediators when stimulated. 1/3 is reserved in spleen for hemmorage, Life span of 9-10 days, thrombopoetin, made by liver stimulates, platelet production by bone marrow====

====**Spleen:** site for fetal //hematopoiesis// (stem cell differentiation), it's local mononuclear //phagocytes filter//(red pulp) remove old RBC's & return iron to bone marrow. Filter bacteria (gram positive). //Immune fuction// (white pulp) lymphocytes, monocytes, and immunoglobulins encounter pathogens. //Storage function//, can store 300 ml of blood and 1/3 of platelets====

**Lymph nodes:** filtration of pathogens and foreign particles that are carried by lymph system,
__//**5. Discuss the role of the colony stimulating factors (CSFs) in the production of blood cells.(lewis, 223-224)(Huether, 490)**//__ Act as growth-regulating factors for hematopoietic cells. Stimulate progeny cells ( after differentiation) to proliferate and then to mature.


 * 6. Explain erythropoiesis and the role of erythropoietin in this process.****(MS p667, patho p491, ppt p9)**

Several distinct cell types evolve during erythrocyte maturation (see [|Fig. 30-1]). The **reticulocyte** is an immature erythrocyte. The reticulocyte count measures the rate at which new RBCs appear in the circulation. Reticulocytes can develop into mature RBCs within 48 hours of release into circulation. Therefore assessing the number of reticulocytes is a useful means of evaluating the rate and adequacy of erythrocyte production.
 * Erythropoiesis** (the process of RBC production) is regulated by cellular oxygen requirements and general metabolic activity. Erythropoiesis is stimulated by hypoxia and controlled by //erythropoietin,// a glycoprotein growth factor synthesized and released by the kidney. Erythropoietin stimulates the bone marrow to increase erythrocyte production. Normally the bone marrow releases 3 × 109 RBCs/kg of body weight per day. Erythropoiesis is also influenced by the availability of nutrients. Many essential nutrients are necessary for erythropoiesis, including protein, iron, folate (folic acid), cobalamin (vitamin B12), riboflavin (vitamin B2), and pyridoxine (vitamin B6). Erythrocyte production is also affected by endocrine hormones, such as thyroxine, corticosteroids, and testosterone. For example, hypothyroidism can be the cause of a microcytic anemia.


 * 7. List the nutrients required for erythropoiesis to take place and explain their function.****(ppt p 10, patho p494 table19-4)**
 * ~ Nutrient ||~ Role in Erythropoiesis ||~ Consequence of Deficiency (see [|Chapter 20]) ||
 * Protein (amino acids) || Structural component of plasma membrane || Decreased strength, elasticity, and flexibility of membrane; hemolytic anemia ||
 * || Synthesis of hemoglobin || Decreased erythropoiesis and life span of erythrocytes ||
 * Intrinsic factor || Gastrointestinal absorption of vitamin B12 || Pernicious anemia ||
 * Cobalamin (vitamin B12) || Synthesis of DNA, maturation of erythrocytes, facilitator of folate metabolism || Macrocytic (megaloblastic) anemia ||
 * Folate (folic acid) || Synthesis of DNA and RNA, maturation of erythrocytes || Macrocytic (megaloblastic) anemia ||
 * Vitamin B6 (pyridoxine) || Heme synthesis, possibly increases folate metabolism || Hypochromic-microcytic anemia ||
 * Vitamin B2 (riboflavin) || Oxidative reactions || Normochromic-normocytic anemia ||
 * Vitamin C (ascorbic acid) || Iron metabolism, acts as a reducing agent to maintain iron in its ferrous (Fe++) form || Normochromic-normocytic anemia ||
 * Pantothenic acid || Heme synthesis || Unknown in humans[|*] ||
 * Niacin || None, but needed for respiration in mature erythrocytes || Unknown in humans ||
 * Vitamin E || Synthesis of heme; possible protection against oxidative damage in mature erythrocytes || Hemolytic anemia with increased cell membrane fragility; shortens life span of erythrocytes in individual with cystic fibrosis ||
 * Iron || Hemoglobin synthesis || Iron-deficiency anemia ||
 * Copper || Structural component of plasma membrane || Hypochromic-microcytic anemia ||


 * 8. Examine the processes of platelet degranulation (see patho p 497 fig. 19-16) and lysis of a clot (patho p 500, MS p 670).**

Just as some blood elements foster coagulation //(procoagulants),// others interfere with clotting //(anticoagulants)//. This countermechanism to blood clotting serves to keep blood in its fluid state. Anticoagulation may be achieved by two means, antithrombins and fibrinolysis. As the name implies, antithrombins keep blood in a fluid state by antagonizing thrombin, a powerful coagulant. Endogenous heparin is an example of an anticoagulant. Other anticoagulants are protein C and protein S. The second means of maintaining blood in its fluid form is **fibrinolysis,** a process resulting in the dissolution of the fibrin clot. The fibrinolytic system is initiated when plasminogen is activated to plasmin (see [|Fig. 30-6]). Thrombin is one of the substances that can activate the conversion of plasminogen to plasmin, thereby promoting fibrinolysis. The plasmin attacks either fibrin or fibrinogen by splitting the molecules into smaller elements known as //fibrin split products// (FSPs) or //fibrin degradation products// (FDPs)
 * clot lysis**

9. Examine the diagnostics utilized to evaluate the hematologic system and relate abnormalities to various disease processes.

10. Describe the general clinical manifestations and potential complications associated with anemia.

11. Examine the compensatory mechanisms that occur in the presence of anemia.

12. Discuss the pathophysiology of hemolytic anemia (alloimmune disease) of the newborn.

13. Describe the etiology, pathophysiology, clinical manifestations and collaborative management of the microcytic-hypochromic anemia, specifically iron deficiency anemia.

14. Describe the etiology, pathophysiology, clinical manifestations and collaborative of the macrocytic-normochromic anemia, specifically folate deficiency anemia.

15. Analyze the predisposing conditions, pathophysiology, clinical manifestations, diagnostic findings, and collaborative management related to disseminated intravascular coagulation. -The common pathway is excessive and widespread exposure of tissue factor (TF or tissue thromboplastin) -TF contribute to conversion of prothrombin to thrombin; the most powerful coagulant -Thrombin catalyzes the conversion of fibrinogen to fibrin & enhances platelet aggregation -Widespread fibrin & platelets in capillaries & arterioles can result in thrombosis, which can lead to tissue ischemia, then multi-organ failure -Excessive clotting activates the fibrinolytic system-that breaks down clots, causing **fibrin split products**-which inhibit clotting & promote bleeding by *coating platelets & interfere w/ their fxn *interfere w/ thrombin *attach to fibrinogen-leading to inability to form clot -This massive clotting event leads to; *excessive platelet aggregation leads to thrombocytopenia *excessive clotting leads to depletion of clotting factors *hemorrhage for all the above reasons *loss of Hgb & O2 carrying capacities *inflammation and complement (go hand in hand w/ clotting sys), leading to platelet destruction (induced by complement system) and increased permeability, tissue dmge, ect. -**Signs of microvascular thrombosis;** result of fibrin or platelet deposition in the microvasculature; Neurologic; multifocal, delirium, coma Integumentary; cyanosis, ischemic tissue necrosis (gangrene),hemorrhagic necrosis Renal; kidney dmge-cortical necrosis, oliguria, azotemia, eventual failure Resp; tachypnea, dyspnea, pulm emboli, ARDS Cardiac; ECG changes, venous distension GI; abd pain, paralytic ileus Neurologic; Intracerebral bleeding, vision changes, dizziness, irritability, HA, ALOC Integumentary; Petechiae (on abd & extremeties), pallor, purpura, ecchymoses, venipuncture site bleeding, oozing blood, hematomas Mucous membranes; epistaxis, gingival oozing Renal; Hematuria Resp; Resp congestion, dyspnea, hemoptysis, tachypnea, orthopnea Cardiac; Tacchycardia, HTN GI; massive bleeding, blood in stool, abd distension Musculoskeletal; bone and joint pain -Prolonged **PT** and **PTT-** prolonged bleeding times, measured in seconds, should be increased -Decreased **Fibrinogen** levels -Increased **Fibrin Split Products** - D Dimer Assay; Increased; D Dimer is a spec. polymer resulting from the breakdown of fibrin (this is a **specific marker** or fibrinolysis) -stabilize pt if needed (O2, volume replacement) -institute therapy that will resolve underlying causative disease -treat s/s (blood products, anticoagulants- both a little controversial) 16. Describe the complication HELLP as it relates to pregnancy and discuss the pathophysiology, clinical manifestations and potential complications. Hemolysis, Elevated Liver Enzymes; AST levels >70 u/L Low Platelets; <100,000 u/L -Variation of Pregnancy induced HTN; sometimes but not always assoc w/ eclampsia and preeclampsia-in 3rd trimester, Progresses to epigastric pain, blurred vision, fluid in lungs, increased bilirubin levels-from massive hemolysis
 * (Lewis 710-713, Huether 540-544, p.point, 17-19, Pili 417) **
 * DIC; predisposing conditions; ** DIC is not a disease it is an abnormal response of the clotting cascade stimulated by a disease process or disorder. For complete list see **Table 31-19 Lewis 710, and Box 20-2 Huether 541.** Some examples are Sepsis from infectious disease is **most common**, Shock, Hemolytic; blood transfusions, acute hemolysis, Obstetric conditions; retained dead fetus, abruptio placentae, Malignancies; Leukemia, lymphoma, Tissue damage; burns, trauma, heatstroke, transplant rejection, and some chronic conditions; liver disease, lupus, ECT.
 * Pathophysiology; ( ** p. point follows Lewis)
 * - ** There may be one or more triggering events that activate the clotting system
 * During this all, natural anticoagulants are depressed; antithrombin III, protein C & S (Can be assessed in lab)
 * Clinical Manifestations DIC; ( ** Lewis 711 fig 31-10, Huether 543 box 20-3) Symptoms are not well defined for DIC; but there can be both thrombotic and bleeding manifestations
 * -Signs of hemorrhage; ** result from consumption & depletion of platelets and coagulation factors, as well as clot lysis and formation of fibrin split products that have anticoagulant properties
 * Diagnostic tests & findings (table 31-20 Lewis 712) **
 * In general; ** *** tests that measure raw materials needed for coagulation are reduced and values that measure times to clot are prolonged** *
 * -Platelet count ** ; **Normal**; 150,000-450,000; high in early stages, decreased later (thrombocytopenia)
 * - ** Decreased Natural anticoagulants;
 * **Proteins C & S, Antithrombin III**
 * Collaborative Mgmt; ** not too specific here;
 * with fresh frozen plasma, can be “adding fuel to the fire” if actively clotting, but is only method to avoid fatal hemorrhage sometimes
 * in general platelets are given for thrombocytopenia if below 20,000uL or 50,000uL w/ bleeding, Cryoprecipitate is given to replace factor VIII, and Fibrinogen is given if levels are <100 mg/dL
 * Normally a person w/ thrombosis is given heparin, this is controversial, for obvious reasons
 * (p.point 19-20, Pili 433, Huether 538) **
 * HELLP; **
 * Mild preeclampsia; 140/90 w/ 1+ or 2+ proteinuria & edema
 * Severe preeclampsia; 160/110 w/ 3+ or 4+ proteinuria and more edema
 * Eclampsia; seizure
 * Pathophysiology **; don’t really understand; may be due to vasospasm. Underlying vascular constriction of hepatic liver bed
 * Clinical Manifestations **
 * First symptoms; ** nausea, tenderness in RUQ(over liver), malaise, HA
 * Potential Complications; **anemia, abruptio placenta, liver damage &pot failure, Ischemia; CVA, ACS, Renal injury, Pulmonary, DIC, Mom/baby death