PATH 370 Week 2 Outline PDF

Week 2 **[Chapter 10]** - Know all hypersensitivity types - There are four (4) types of hypersensitivity: - Type I hypersensitivity - Also known as "immediate hypersensitivity," "atopic hypersensitivity," or "anaphylactic hypersensitivity"...

Week 2 **[Chapter 10]** - Know all hypersensitivity types - There are four (4) types of hypersensitivity: - Type I hypersensitivity - Also known as "immediate hypersensitivity," "atopic hypersensitivity," or "anaphylactic hypersensitivity" - Response of IgE to antigens or allergens - Usually has a strong genetic or hereditary linkage - Allergic reaction usually occurs between 15 and 30 minutes - IgE is produced by specialized plasma B cells - B cells create and release IgE, which then affects mast cells - IgE antibodies on mast cells are bound by an antigen that links with an IgE receptor - Mast cells degranulate and release chemicals like histamine, kinin, prostaglandins, interleukins, and leukotrienes - This release of chemicals causes vascular permeability, vasodilation, hypotension, urticaria, and bronchoconstriction - Type II hypersensitivity - Also known as "cytotoxic hypersensitivity," or "cytolytic hypersensitivity" - Antibodies form against antigens on cell surfaces that result in lysis of the target cells - Lysis is mediated by IgM and IgG activated complement fragments, or by phagocytotic cells that are attracted to target cells by attached antibodies - Allergic reaction usually occurs in 15 to 30 minutes - These reactions are indicative of transfusion reactions, erythroblastosis fetalis, myasthenia gravis, and hyperacute graft rejection - Type III hypersensitivity - Also known as "immune complex hypersensitivity" or "arthus reaction" - An antigen-antibody complex is deposited into tissue and the complement is activated as a result, which causes tissue inflammation - This type of reaction is mediated by IgG antibodies - A complement cascade reaction happens, which brings phagocytotic cells to the tissue - Symptoms include low grade fever, antigen inhalation - This type of reaction occurs about 6 hours after exposure - Examples are glomerulonephritis, lupus, farmer's lung arthritis, and vasculitis - Type IV hypersensitivity - Type IV hypersensitivity is the only type of hypersensitivity that does not involve antigens or antibodies, but instead is mediated by T-cells, which is different from all other types of hypersensitivity - Sensitized T-cells react with altered cells or foreign cells or foreign bodies and cause inflammation, specifically in the dermal region - This type of hypersensitivity takes about 24 to 48 hours - Examples are contact dermatitis, tuberculin reactions, transplantation reactions, Guillain-Barre Syndrome, and multiple sclerosis **[Chapter 11]** - Know all information on the following: ALL, CML, Multiple Myeloma, Hairy Cell Leukemia - Acute Lymphoblastic Leukemia or Lymphoma (ALL) - Facts about ALL - Leukemias are in the blood, lymphomas are in the lymphatic system, regardless of where they originated - Extremely malignant form from the lymphoid cell lineage - Lymphoid neoplasms involve transformations of the lymphoid cells: B-cells, T-cells, and NK cell - Etiology -- Mutation of lymphoid B-cells, T-cells, or NK cells - Pathogenesis - 80% of ALL cases are malignant transformation of B-cells. The other remaining 20% are cases of malignant transformation of T-cells. - Abnormal ALL cells look like lymphoblasts in the immature stage and affect the immature cell - Since this ALL acute, it impacts immature cells - There are different considerations for lymphoblastic lymphoma versus lymphoblastic leukemia and it is believed that they are manifestations of the same disease at different stages - Clinical Manifestations - ALL is primarily a children's disease, where peak incidence is 3 to 7 years of age, and there can be a second peak in middle age - ALL has an abrupt onset - Symptoms include: - Bone pain - Bruising - Fever - Infection - Refusal to walk - Loss of appetite - Fatigue - Abdominal pain - Enlarged spleen - Enlarged liver - Enlarged lymph nodes - Central nervous system signs - Treatment - Prognosis is good, where there is an 85% 5-year prognosis in children, and 30 to 50% in adults - ALL is mostly responsive to chemotherapy - Stem cell transplantation and chemotherapy is usually indicated - Monoclonal antibodies for immunotherapy may be used - Chronic Myeloid Leukemia (CML) - Myeloid Neoplasm - Facts about CML - 15% of all leukemias are CML - Affects an older population (40 to 50 years of age) and more men than women - Rarely occurs in childhood or adolescence - Usually affects neutrophils, but can affect any granulocyte - Etiology -- Due to transformation and proliferation of a precursor stem cell in the bone marrow that gets released into the bloodstream as mutant cells - Pathogenesis -- Malignant granulocytes have a specific abnormality on the Philadelphia chromosome (Ph+). - The Ph+ chromosome has a translocation of chromosomes 9 and 22, which creates the fusion gene BCR-ABL. - Manipulation of the BCR-ABL gene inhibits apoptotic cell death - CML cells are mature compared to AML cells and is noted by greater nucleus segmentation - Mature cells are what gives it the designation as "chronic" - Clinical Manifestations - High granulocyte count on CBC - Splenomegaly - Symptoms include: - Fatigue - Weight loss - Sweats - Bleeding - Abdominal discomfort (due to enlarged spleen) - Treatment - Treatment is generally not useful and CML does not respond well to chemotherapy. Life expectancy is low after discovering CML - Anti BCR-ABL therapy can reduce the number of BCR-ABL cells in the body to undetectable levels - Allogenic bone marrow transplantation can be performed - Multiple Myeloma (Plasma Cell Myeloma) - Facts about Multiple Myeloma - A malignant disorder of mature B-cells, otherwise known as plasma cells - Multiple myeloma tends to invade bone cells and forms tumors in the bone tissue - Although Multiple Myeloma mainly affects bone tissue, it still is able to be found in different parts of the body, like the lymph nodes, the liver, the spleen, and the kidneys - Multiple Myeloma exclusively occurs in adults, usually over the age of 40 - Etiology -- Due to malignant mutation of B-cells with a chromosomal structure and chromosomal abnormality disorder potentially linked - Pathogenesis - Multiple Myeloma arises from a single mutated, high replicating plasma cell - The mutated plasma cell produces excessive amounts of monoclonal antibodies - Clinical Manifestations - The Bence-Jones protein is produced by malignant plasma cells that accumulate in the blood and urine, which can damage the kidneys because these proteins in high amount are not intended to pass the basement membrane of the kidney - Malignant plasma cells also accumulate in the bone tissue and lead to pathological fractures due to bone destruction - This bone destruction also releases calcium into the blood stream, which leads to hypercalcemia, which is detected in blood tests - The most prevalent clinical manifestations are bone damage and renal damage - Bone involvement ends with a honeycomb appearance where the bone has been degraded - This usually occurs in the skull, spinal column, ribs, and pelvis - Treatment - There is no good treatment for Multiple Myeloma - Antineoplastic agents are used, chemotherapy is not established, but chemotherapy with bone marrow transplantation is sued - Treatment of renal damage to avoid excessive kidney damage or kidney failure is done supportively - Hallmark - Hairy Cell Leukemia - Facts about Hairy Cell Leukemia - It is a rare adult leukemia and is considered chronic - It is highly treatable - Affects the population of a median age of 55, which are mostly male - Only affects B-cells - Etiology -- Malignant mutation of B-cell - Pathogenesis - There is a reduced number of granulocytes, number of platelets, and number of red blood cells - Peripheral blood smears show B-cells that look hairy in appearance - 90% of patients experience splenomegaly - Clinical Manifestations - Symptom onset is when hairy cell leukemia is usually identified - Symptoms include: - Enlarged spleen - Recurring infection - Bleeding disorder - Anemia - Treatment - Treatment with chemotherapy protocol - Autologous vs. Allogenic Bone Marrow Transplant - Autologous bone marrow transplant is the use of a patient's own bone marrow that is harvested and reintroduced into the bone marrow space after some type of cancer treatment, such as chemotherapy or radiation on a specific area. Allogenic bone marrow transplant is the transplantation of bone marrow from a donor who has very close similarity in makeup that allows for the bone marrow to be introduced with low risk of rejection. - Allogenic bone marrow transplant is usually a better option if it is available, because it is known that there are no malignant bone marrow cells present when reintroducing the bone marrow to the patient. In autologous bone marrow transplant, it is possible that a malignant cell is present or may become introduced, and this type of transplantation should be used with an abundance of caution. **[Chapter 13]** - Transfusion reactions involve RBC destruction caused by recipient antibodies - Red blood cells have no cytoplasmic organelles - Iron deficiency has low MCHC (mean corpuscular hemoglobin concentration), MCH (mean corpuscular hemoglobin), and MCV (mean corpuscular volume) - Carbon dioxide is transported in the bloodstream as bicarbonate ion - Bilirubin can detect excessive red blood cell lysis - Kidneys produce erythropoietin - Iron is necessary for red blood cell production - Iron deficiency leads to pale color, mycrocytic red blood cells (small red blood cells), and low MCV, MCH, MCHC - Aplastic Anemia leads to pancytopenia - Aplastic anemia is acquired and is due to a reduction in hematopoeitic tissue, where bone marrow volume is reduced. This means that all blood constituents are not being synthesized properly, leading to pancytopenia - This is caused by toxic injury, radiant injury, or immunological injury to bone marrow stem cells - Pernicious anemia is caused by lack of intrinsic factor - Glucose-6-phosphate dehydrogenase deficiency anemia occurs when exposed to certain drugs - Glucose-6-phosphase dehydrogenase is a protein that is used to decrease oxygen affinity with red blood cells. This enzyme allows more oxygen to stay in the blood and tissues by preventing bonding of oxygen to hemoglobin, reducing hemoglobin's affinity - Know functions of the circulatory system - The circulatory system is used to transport gases and remove metabolic wastes from the capillaries - Disruption in the circulatory system leads to ischemia and hypoxia as a result - When oxygen carrying capacity is reduced, compensation occurs where the heart rate is increased, cardiac output is increased, circulatory rate is increased, and flow to vital organs is increased **[Chapter 14]** - Hemophilia: prolonged bleeding time, prolonged aPTT, normal platelet count - Hemophilia is the most common inherited coagulation disorder that causes excessive bleeding - There are two types of hemophilia: - Hemophilia A: Factor VIII deficiency - Hemophilia B: Factory IX deficiency - The aPTT test is the activated partial thromboplastin test that measures the time for clotting. High aPTT test means it takes longer than normal for blood to clot. - Hemophilic patients are fragile and can experience excessive bleeding due to internal injury - Vitamin K deficiency in newborns present with melena, bleeding from the umbilicus, and hematuria. - Vitamin K deficiency is acquired - Vitamin K deficiency reduces the amount of coagulation factors that can by synthesized since Vitamin K is an essential component of Factors II, VII, IX, and X - Melena is blood in the stool of a newborn, which is abnormal - Vitamin K deficiency: normal bleeding time, normal platelet count, increased PT and INR - PT is Prothrombin Time. INR is International Normalized Ratio. These two numbers are used to determine if blood is clotting normally. A high PT/INR value means that there is a deficiency in blood clotting, likely due to Vitamin K deficiency in this circumstance - In adults, this could be due to liver disease, antibiotic therapy, malnutrition, malabsorption, or anticoagulation therapy - Know Blood Coagulation Assessment: PT(Prothrombin Time)/INR (International Normal Ratio)=Extrinsic Pathway, aPTT (activated Partial Thromboplastin Time)=Intrinsic Pathway, Bleeding time - Aspirin can prolong bleeding time - For patients with hemophilia, it is not advised to take aspiring because it can artificially prolong bleeding due to altering platelet function - Chemotherapy can cause thrombocytopenia - Chemotherapy can cause thrombocytopenia because platelet survival and production is reduced since bone marrow is a high-turnover cell type - Know DIC (disseminated intravascular coagulation) - DIC is acquired - Bleeding and clotting occur simultaneously and is a hemorrhagic syndrome - There is reduced fibrinogen and reduced platelet count that leads to increased bleeding time since the right proteins are not in place to create a plug or contribute to hemostasis - Patients have elevated PT/INR, elevated aPTT, and elevated d-dimer - D-dimer measures the amount of fibrin that is in the blood - Dysfunction of the liver can lead to clotting factor deficiency - The liver is responsible for synthesis of many clotting factors, so deficiency in its function can lead to issues in the cardiovascular system **[Chapter 15]** - Venous vs. Arterial occlusion - Arterial occlusions lead to ischemia - Venous occlusions lead to edema - Thrombosis vs. Embolism - A thrombus is a stationary clot that is formed from slowed blood flow and subsequent accumulation of blood products - An embolus is a clot that has broken free and is floating throughout the circulatory system - An embolus that leaves the left ventricle can cause an ischemic stroke - An embolus that leaves the right ventricle can cause pulmonary embolism - Peripheral edema is a result of venous thrombosis - Arterial thrombosis leads to ischemia - Venous thrombosis leads to edema - Peripheral edema is due to stagnation of blood due to restricted blood flow in the vein - Atherosclerosis - Atherosclerosis is the formation of plaque and subsequent thickening and hardening of the arteries - There are three types of scleroses: - Manckeberg - Arteriolar - Athero - There is usually an underlying cause of atherosclerosis - Hypertension, cardiac disease, renal disease, peripheral artery disease, stroke, low LDL and high HDL - Atherosclerosis occurs when platelets gather and release growth factor to encapsulate a lipid that is in the arterial wall. Platelets then stimulate the growth of the smooth muscle cells. The platelets then form a plaque around the lipid, decreasing the lumen size and reducing blood flow and perfusion to tissues - DVT vs. Varicose Veins - Varicose veins are superficial, darkened, raised, and tortuous veins that usually stem from the greater saphenous vein - DVT is a deep vein thrombosis that is found in the veins of the peripheral limbs that restricts blood flow back to the inferior vena cava