Midterm-patho- Hematologic & Cancer – Flashcards

First, the patient should take some comfort in the fact that his tumor is benign. A malignant tumor of the same origin would be a hepatocellular adenocarcinoma. Benign tumors have the following characteristics: slow growth, well-defined capsule, less invasive, well-differentiated, low mitotic index, and do not metastasize. Malignant tumors tend to grow rapidly, lack encapsulation and differentiation, invade local structures, have a high mitotic index, and spread to distant locations through the bloodstream or lymphatics.

Chronic inflammation causes cancer by releasing compounds such as reactive oxygen species that promote mutations.

Chronic inflammation increases the relative risk for many cancers. Toxins released from cigarettes inflame and damage respiratory tissue. Crohn disease can cause extensive chronic inflammation anywhere in the gastrointestinal tract. Working as a farmer requires many days out in the sun. The farmer probably has not had a sunburn in years, but frequent sunburn is not a prerequisite for skin cancer. As was discussed in previous chapters, the inflammatory process causes release of compounds such as reactive oxygen species and molecules that can promote mutations and block the cellular response to DNA damage.

Symptoms of polycythemia vera are mainly the result of increase blood viscosity.

A characteristic of cancer in situ is that cells remain localized in the glandular or squamous cells

Oncogenes are Genes that have undergone mutation that direct the synthesis of protein to accelerate the rate of tissue proliferation Hormones, enzymes, antigens, and antibodies produced by cancer cells are tumor cell markers.

The PSA is a protein produced by the cells of the prostate gland. The PSA test measures the level of PSA in the blood. The PSA test is reported in nanograms per milliliter (ng/ml). It is normal for men to have low levels of PSA in their blood. There is not a specific normal or abnormal level of PSA. PSA levels can increase as a result of prostate cancer or benign prostate conditions. Some of the more common benign prostate conditions are prostatitis and benign prostatic hyperplasia. However, the higher a man's PSA level, the more likely prostate cancer is present. PSA levels alone do not give physicians enough information, but physicians will take the PSA result into account when deciding whether to check further for signs of prostate cancer.

Glucose 6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell disease are both disorders that are initiated by hypoxemia and acidosis.

When patients who have lung cancer develop Cushing syndrome it is an example of a paraneoplastic syndrome.

Hypercalcemia is an electrolyte imbalance that accompanies multiple myeloma

A requirement for localized spread of cancerous cells is angiogenesis. Once tumor cells grow beyond a few millimeters, simple diffusion of oxygen does not provide enough nutrients to meet the needs of the growing cells. More advanced cancer cells can secrete angiogenic factors that activate a cascade of mediators to form new vasculature and provide nutrients to the tumor. With these resources, the tumor can now continue to expand.

Cancers arising from connective tissue usually have the suffix sarcoma. Cancers of lymphatic tissue are called lymphomas, whereas cancers of blood-forming cells are called leukemias. Carcinoma is a cancer of epithelial tissue

Catecholamines are secreted by the adrenal medulla and are found in excess if a tumor exists. PSA levels are used to detect prostate cancer. AFP is used to detect liver and germ cell cancers. ACTH is the marker used to detect pituitary adenomas.

Because subsequent generations were not affected by the cellular mutations, it can be concluded that primarily the somatic cells were affected. If the germ cells were affected, serious congenital conditions would likely have been a result.

Cancer confined to the organ of origin is stage 1; cancer that is locally invasive is stage 2; cancer that has spread to regional structures, such as lymph nodes, is stage 3; and cancer that has spread to distant sites, such as a liver cancer spreading to the lung or prostate cancer spreading to bone, is stage 4. The prognosis generally worsens with increasing tumor size, lymph node involvement, and metastasis. Benign tumors do not spread to distant regions.

Cancer development involves multiple stages including initiation, promotion, and progression. This theory best explains cancers in adults with a 20+-year latency period. In the initiation stage, there is rapid, irreversible altering or mutation of DNA that occurs after a single exposure to a carcinogen (initiator). There must be a strong enough dose or exposure to cause DNA change. In this case, the patient was most likely exposed to ionizing radiation as a child—perhaps inadvertent exposure because of his father's occupation. After this initiation stage, the cells stay dormant in G0 phase or, if dividing, produce very small numbers of transformed daughter cells. The initiated cells are not considered cancerous until a promoting agent acts on them over time to produce an altered, autonomous phenotype. In the promotion stage, promoters induce tumor development. These promoters can be hormones; chemical agents such as drugs, chemicals, tobacco, and plant products; or environmental factors such as air pollution, occupation, diet, and ultraviolet (UV) radiation. For promoters to induce tumor development, there must be time-dependent repeated exposures to the promoters or prolonged exposure over a period of time. Promoters interfere with differentiation and maturation, activating the transformed cell to go through mitotic division, and continue to go through replication phases. In the early stages, the effects of promoters can be reversible. In this case, the patient had a number of possible promoters that contributed to his cancer, including smoking, alcohol use, occupational exposure to fine dust particles, chronic exposure to -radiation, a high-meat and high-fat diet, and polycyclic hydrocarbons produced from charred, barbecued meat. In the progression stage, chromosomal abnormalities are in the cells. The greater the replications, the more the cell becomes abnormal. This leads to tumor development, invasion, and metastasis

The spleen is not necessary for life or for hematologic function. However, several functions related to the spleen are impaired when it is removed. Leukocytosis occurs after the loss of the spleen, indicating that it may play a regulatory role in leukocyte production. Because the spleen has a role in the iron cycle, circulating iron levels decrease when the spleen is lost. Immune function also decreases when the spleen is absent, increasing infection risk. Antibody production diminishes, and old and defective blood cells that were previously removed by the spleen continue to circulate.

Adequate nutrition is necessary to provide the building blocks for erythropoiesis. This includes adequate amounts of protein, vitamins, and minerals. If nutrition is inadequate, the result is a slowing in the production of erythrocytes and subsequent onset of anemia. Protein plays a significant role in erythropoiesis. Inadequate available protein results in decreased erythrocyte production and shortened life span of those erythrocytes that are produced. In the absence of several vitamins, particularly B12 and folate, erythropoiesis is halted.

Hemostasis involves a complex sequence of events. After injury, vasoconstriction or vasospasm constricts the bleeding vessels. This is followed by the formation of a platelet plug. The coagulation or clotting cascade is then activated and results in the formation of a blood clot. As the injury heals, clot retraction (which joins wound edges) and clot dissolution (fibrinolysis) occur.

Aspirin limits platelet aggregation and vasoconstriction by inhibiting synthesis of thromboxane A2, a prostaglandin. Thromboxane A2 is present in the dense granules of platelets and is released as the platelets begin clumping. By taking an aspirin, this decreases the chance of the platelets forming microclots.

The patient has secondary absolute polycythemia. Given the choice, hemoglobin prefers carbon monoxide over oxygen. As the patient smokes, the binding sites for oxygen are taken up by carbon monoxide. Because of the decreased oxygen-carrying capacity, the patient becomes hypoxic. The hypoxia is detected by the kidneys, erythropoietin is released, and more red cells are made to compensate for the lack of oxygen. The patient is now at risk for thrombus and embolus formation, heart failure, coronary artery disease, etc.

Both CGL and ALL are diseases of blood-forming organs causing growth of uncontrolled, undifferentiated, and immature lymphocytes (blast cells). These immature cells then circulate in the blood, infiltrating the liver, spleen, lymph nodes, and other tissue sites. The blood-forming cells affected by ALL and CGL are the lymphoid stem cells. Both CGL and ALL tend to occur in families, suggesting hereditary susceptibility. ALL affects primarily children. It is both an accumulation and a proliferation disorder in which a transformed mutation clones a line of poorly differentiated, abnormal daughter cells. These cells are unable to mature or respond to normal regulatory mechanisms. They also proliferate rapidly, which decreases or stops the proliferation of other cell lines in the bone marrow. ALL affects primarily either T cell or B cell lines. Anemia, thrombocytopenia, hemorrhage, and disseminated intravascular coagulation (DIC) usually accompany ALL. The gonads, bones, joints, central nervous system, kidneys, lungs, and gastrointestinal tract are the most common sites of infiltration. CGL affects primarily B cells in adults. The cells in CGL are slow growing and well differentiated. In CGL the B cells are unable to mature and synthesize immunoglobulin. Therefore individuals with CGL lack humoral immunity and have increased risk of infection, autoimmunity, and the development of secondary cancers. Anemia is usually mild, and hemorrhage is rare. Lymph node, liver, spleen, and salivary gland infiltration is common.

DIC is a cyclic disorder in which massive intravascular coagulation is triggered at the cellular level, producing microthrombi. The microthrombi block the microvascular system, using up clotting factors and platelets as well as causing widespread tissue ischemia. The development of widespread microthrombi formation at the cellular level also activates the fibrinolytic system, which attempts to rapidly lyse the clots. This process releases fibrin degradation or split products (FDP or FSP). The consumption of clotting factors and platelets along with the rising levels of FSP leads to inhibition of coagulation and bleeding. The bleeding with loss of vascular volume also contributes to tissue ischemia.

Children with Hgb S have a genetic hemoglobin mutation in which one amino acid, glutamic acid, is replaced by another amino acid, valine. When stressors such as dehydration, decreased PO2, or decreased pH occur, a sickling cycle follows. Systemic or local decreased PO2 (hypoxemia) causes Hgb S cells to form an elongated crescent shape because of reaggregation of hemoglobin into long chains. This shape causes the red blood cell membranes to become stiff, thus losing some of their capacity for active transport. In a hypoxemic state, sickling is further promoted in the microcirculation when hemoglobin releases oxygen to the tissues, and the microcirculation is clogged by sickled cells. This results in further stagnation and hypoxemia. Acidosis decreases hemoglobin's affinity for oxygen, causing more release of oxygen and contributing to sickling. Acidosis also causes less oxygen to be picked up by circulating hemoglobin in the lungs, further contributing to decreased PO2. Increased osmolality causes sickling because of resultant cellular dehydration and increased Hgb S content within the cells. Increased osmolality also causes sluggish blood flow, contributing to hypoxemia, vascular obstruction, and further sickling. In reversible sickle cells, the membranes will return to normal when the PO2 of the blood returns to normal. In irreversible sickle cells, the membranes stay in the elongated crescent shape because of calcium ion influx.

Chronic inflammation causes cancer by releasing compounds such as reactive oxygen species that promote mutations.

Symptoms of polycythemia vera are mainly the result of increase blood viscosity.

A characteristic of cancer in situ is that cells remain localized in the glandular or squamous cells.

Oncogenes are Genes that have undergone mutation that direct the synthesis of protein to accelerate the rate of tissue proliferation

Hormones, enzymes, antigens, and antibodies produced by cancer cells are tumor cell markers.

Benign tumors have a low mitotic index.

Glucose 6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell disease are both disorders that are initiated by hypoxemia and acidosis.

Platelets are formed elements of the blood that are not cells, but disk-shaped cytoplasmic fragments essential for blood clotting.

Cancers arising from connective tissue usually have the suffix sarcoma.

lymhoma

Leukemias

Carcinoma

Stage 1: Cancer confined to the organ of origin Stage 2: cancer that is locally invasive is stage Stage 3: cancer that has spread to regional structures, such as lymph nodes Stage 4: cancer that has spread to distant sites, such as a liver cancer spreading to the lung or prostate cancer spreading to bone, is stage 4. The prognosis generally worsens with increasing tumor size, lymph node involvement, and metastasis. Benign tumors do not spread to distant regions.

Two distinct mechanisms give rise to patterns of distant spread. First, cancer cells spread through vascular and lymphatic pathways, as well as natural tissue planes. Metastatic cells are very heterogeneous, and some of these cells have new abilities that can facilitate metastasis. Metastasis is highly inefficient; to metastasize, a cancer cell must surmount multiple physical and physiologic barriers. Many metastatic cells secrete proteases and protease activators to digest the extracellular matrix and basement membrane, enabling cells to move. Only rare cells in a cancer are able to metastasize.

Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin disease.

Erythrocytes carry hemoglobin, are responsible for tissue oxygenation, and do not have a nucleus or mitochondria; therefore they cannot divide or synthesize proteins. These cells make up 42% to 48% of blood volume.

The fibrinolytic system breaks down blood clots.

Nitric oxide causes vasodilation.

The extrinsic pathway is activated when tissue factor is released from damaged endothelial cells.

Antithrombin III is a circulating plasma protease inhibitor that inhibits thrombin and factor Xa.

Macrocytic anemias are characterized by unusually large stem cells (megaloblasts) in the marrow that mature into unusually large cells (macrocytes) in the circulation. These cells have increased size, thickness, and volume. These anemias are the result of defective erythrocyte deoxyribonucleic acid (DNA) synthesis, which is commonly caused by deficiencies of vitamin B12(cobalamin) or folate (folic acid) or defective coenzymes that are required for nuclear maturation and DNA synthesis.

Aplastic anemia occurs with pancytopenia, which is a decrease in all three cell types. (Hereditary hemochromatosis (HH), Myelodysplastic syndrome)

Hereditary hemochromatosis (HH) is a common inherited, autosomal recessive disorder of iron metabolism and is characterized by increased gastrointestinal iron absorption with subsequent tissue iron.

Myelodysplastic syndrome is a group of disorders that demonstrate hematopoietic stem cell dysfunction. A defect of mitochondrial heme synthesis causes sideroblastic anemia.

The most common leukemia in children is ALL, and it represents 78% of leukemias in children. It often occurs in the first decade of life.

The peak incidence of Hodgkin lymphoma occurs during the early 20s through the 30s and again in the sixth and seventh decades of life. The incidence is greater in whites, and Japan and Australia have the lowest incidence. An increase in Reed-Sternberg cells occurs.

ITP is an immune process that involves autoantibodies. Chronic ITP is more commonly observed in adults. Initial manifestations are usually minor problems such as petechiae that progress to major hemorrhage from mucosal sites. The acute form of ITP is frequently observed in children and typically lasts 1 to 2 months with a complete remission.

Sickle cell disease is an autosomal recessive disorder that is most common in central Africa, the Near East, the Mediterranean, and part of India. Sickle cell trait has one hemoglobin S (HbS) gene and one normal HgA gene. In sickle cell disease, a person has two HbS genes, which represents the homozygous form of this disease.

Vaso-occlusive crisis may spontaneously develop or be precipitated by infection, cold temperatures, dehydration, or low pH. This condition occurs when the cells clump and occlude vessels. Sequestration crisis is when large amounts of the blood become pooled in the liver and spleen. Hyperhemolytic crisis is unusual and often occurs with the concomitant presence of G6PD.