Term
| The blood vascular system is __________ and ________, while the lymphatic system is _______-________ and __________ |
|
Definition
-circular and closed
-open-ended and linear |
|
|
Term
| lymphatics maintain the pressure in the _______-________ fluid |
|
Definition
|
|
Term
| Plasma makes up _____% of blood and cells make up _____% |
|
Definition
|
|
Term
| Where does hematopoiesis take place in an embryo, fetus, young child, and adult? |
|
Definition
embryo= yolk sac, liver, spleen
fetus= bones, liver, spleen
child= all your bones
adult= just the flat and short bones of the axial skeleton |
|
|
Term
| What is associated with each of the hematopoietic diseases: red cell disorders, white cell disorders, and platelet disorders? |
|
Definition
RBC= anemia
WBC= neoplasia
platelets= bleeding |
|
|
Term
| Define anemia and polycythemia |
|
Definition
-anemia= a reduction in the oxygen-transporting capacity of blood (usually due to too few RBC's)
-polycythemia= an increase in the number of RBCs |
|
|
Term
| What are the three classifications of anemias based on cause? |
|
Definition
-blood loss (hemorrhage)
-increased RBC destruction (hemolysis)
-decreased RBC production |
|
|
Term
| WHat are the three classifications of anemias based on morphology (cell size)? give two examples of each. |
|
Definition
-microcytic (ex: iron deficiency, thalasemia)
-macrocytic (ex: folate or B12 deficiency)
-normocytic, but abnormally shaped (ex: hereditary spherocytosis, sickle cell disease) |
|
|
Term
| What are the two classifications of anemias based on color? |
|
Definition
-normochromic
-hypochromic
**degree of hemoglobinization |
|
|
Term
| Describe the clinical manifestations of acute, chronic (hemolysis), and chronic (defective erythropoiesis) classifications of anemias. |
|
Definition
-Acute: SOB, organ failure, shock
-Chronic (hemolysis): skeletal abnormalities (bc of bone marrow expansion); growth retardation; jaundice and gallstones
-Chronic (defective erythropoiesis): iron overload, heart and endocrine failure |
|
|
Term
| Anemias of blood loss are due to __________ |
|
Definition
|
|
Term
Describe acute blood loss leading to anemia in 3 main points:
-what is the immediate threat?
-describe the RBC's in this type of anemia
-What enhances recovery? |
|
Definition
-Immediate threat is hypovolemic shock (heart is unable to pump what is left after severe blood and fluid loss)
-Anemia is normocytic and normochromic (there is nothing wrong with these RBCs, they're just exiting the body before they can be replenished)
-Recovery is enhanced by increased erythropoiesis |
|
|
Term
Describe chronic blood loss leading to anemia in three main points:
-what happens to the iron stores ?
-what is iron required for?
-This leads to chronic anemia of _____________/____________ |
|
Definition
-iron stores are gradually depleted (we need iron to carry oxygen to the body and to make RBCs)
-iron is required for erythropoiesis
-leads to chronic anemia of DIMINISHED ERYTHROPOIESIS |
|
|
Term
| Hereditary spherocytosis is a defect in the RBC _________ that makes cells _________ in shape and vulnerable to ____________ in the _____________ |
|
Definition
membrane
spherical
destruction
spleen |
|
|
Term
| Hereditary spherocytosis can lead to three disorders, what are they? |
|
Definition
anemia
splenomegaly
jaundice |
|
|
Term
| Hereditary spherocytosis is common in people of what ancestry? |
|
Definition
Northern European
1 in 2,000 people |
|
|
Term
| Hereditary spherocytosis is due to mutations in possibly one of five different genes. 50% of cases are due to mutations in what gene? Mutations in these gene are transmitted in what manner?? |
|
Definition
-ankyrin 1, erythrocytic (ANK1) gene
-transmitted in an AUTOSOMAL DOMINANT manner (but can also occur spontaneously in many indvdls) |
|
|
Term
| What is the function of membrane proteins in RBCs? What is the problem in hereditary spherocytosis? |
|
Definition
-they maintain stability of RBCs and allow for their flexibility
-Mutations in membrane proteins (mainly ANK1, like in hereditary spherocytosis), result in loss of membrane fragments, cell then adopts a spherical shape, and is trapped and destroyed by the spleen.
*RBCs trapped in the spleen can cause splenomegaly |
|
|
Term
| What are the most common single-gene diseases in humans and cause substantial morbidity? |
|
Definition
| -hemoglobinopathies (genetic disorders of hemoglobin) |
|
|
Term
| Hemoglobin was one of the first protein structures to be _________. |
|
Definition
|
|
Term
| The WHO estimates the _____% of the world's population are carriers of genes for clinically important disorders of ________ |
|
Definition
|
|
Term
| What are the 4 subunits of an adult hemoglobin? |
|
Definition
-two alpha polypeptide chains
-two beta polypeptide chains |
|
|
Term
| each of the subunits on an adult hemoglobin has a prosthetic group, what is its function? |
|
Definition
-prosthetic (HEME) group
-heme is an iron-containing pigment that combines with O2 to give the molecule its O2-transporting ability |
|
|
Term
| In addition to adult hub (HbA), there are how many other normal human hemoglobins? |
|
Definition
5
each consists of two alpha (or alpha like) chains (chr 16) and two beta (or beta like) chains (Chr 11) |
|
|
Term
| The alpha globin gene is expressed in ________ and in _________. What chromosome is it associated with? |
|
Definition
|
|
Term
| What are nonfunctional genes that are closely related (by DNA sequence) to functional genes present elsewhere in the genome? |
|
Definition
|
|
Term
| How do pseudogenes arise? |
|
Definition
| -by gene duplication, followed by the acquisition of DNA mutations that render it non-functional |
|
|
Term
| The beta globin gene and the gamma genes are located on chromosome ______. How much are each expressed in fetus and in adult? |
|
Definition
11
-betas= low in fetus and high in adult
-gammas= high in fetus and low in adult |
|
|
Term
| What causes hemoglobin structural variants? How many hgb variants have been identified? |
|
Definition
-alpha and beta globins with variant amino acid sequences (usually single DNA changes that cause single amino acid changes)
-more than 400 have been identified |
|
|
Term
| What is wrong with the hemoglobin of a patient with Thalassemia? |
|
Definition
| they have decreased synthesis of one or more of the globin chains, resulting in an imbalance in the relative amounts of the alpha and beta chains |
|
|
Term
| Describe the issue with the hgb of a patient with hereditary persistence of fetal hgb. |
|
Definition
-the perinatal switch from gamma-globin to beta-globin synthesis is impaired
-they are clinically benign conditions |
|
|
Term
Which molecular disease was the first example of inherited variation in protein structure?
-it was the first direct proof that mutations in DNA result in a change in ________/_________/_________ in proteins
-it showed evidence that change in a single _________ of DNA can cause a genetic disorder |
|
Definition
-Sickle cell anemia
-amino acid sequence
-nucleotide |
|
|
Term
| Sickle cell anemia is due to a _________ mutation in the ______ globin gene |
|
Definition
|
|
Term
| THe pathogenesis of sickle cell anemia includes the polymerization of beta globin to form ________ |
|
Definition
|
|
Term
Fetal hemoglobin (HbF) has two alpha globins and two _______ globins.
What happens to the gamma globins at birth? |
|
Definition
gamma
they are switched off at birth and the beta gene is activated |
|
|
Term
| Treatment with an _______ drug (drug name?) reactivates gamma genes. |
|
Definition
anticancer-->hydroxyurea
fetal hgb then reappears in RBCs |
|
|
Term
Thalassemias are associated with an imbalance in the production of what?
Due to this, these hgb's do not bind _________ efficiently and can be lethal |
|
Definition
-alpha or beta globin
-causes the formation of hgb molecules with an abnormal number of alpha or beta globins
-OXYGEN |
|
|
Term
| What is alpha thalassemia and what is the most common cause? |
|
Definition
-reduced or absent synthesis of alpha globin
-most common cause is deletion of one or both alpha globin genes |
|
|
Term
| What is beta thalassemia and what is the most common cause? |
|
Definition
-reduced or absent synthesis of beta globin
-most common cause is single-base pair substitutions that result in proteins that have either reduced activity, altered activity, or no activity at all |
|
|
Term
| Genetic disorders of alpha-globin production affect the formation both _______ and _______hemoglobins. |
|
Definition
|
|
Term
| In the absence of alpha-globin chains, the chains from the B-globin cluster form __________ hemoglobins, which are incapable of releasing _________ to tissues in normal conditions |
|
Definition
|
|
Term
| Two examples of A-thalassemias are Hb H (B4) disease and Hydrops Fetalis, Gb Bart's (G4). Explain each. |
|
Definition
-Hb H (beta 4)= a moderately severe hemolytic anemia develops bc of the gradual precipitation of the Hb H in the erythrocyte. Leads to the formation of inclusions in the mature RBC, and the removal of these inclusions by the spleen damages the cells, leading to their premature destruction
-Hb Bart's (gamma 4)- infants suffer from severe intrauterine hypoxia and are born with massive generalized fluid accumulation |
|
|
Term
| Genetic disorders of Beta-globin production affect the formation of hgb's only in the __________ period. |
|
Definition
|
|
Term
| The most common forms of B-thalassemia are the result of _______-_______/_________ substitutions |
|
Definition
|
|
Term
| In Beta thalassemias, Decreased B-globin production leads to imbalance in globin synthesis and the precipitation of the excess normal alpha chains to form a _________/_______ in the RBC, which in turn leads to damage of the RBC membrane |
|
Definition
|
|
Term
| In regions of the world where B-thalassemia is common, individuals may be _________/_________ for two different B-thalassemia alleles and have thalassemia _________. What is this condition characterized by? |
|
Definition
compound heterozygotes
major
-characterized by SEVERE anemia and the need for lifelong medical management |
|
|
Term
| Carriers of one B-thalassemia allele are clinically well and have thalassemia _________. What is this condition characterized by: describe the RBCs, what is it initially often times misdiagnosed as? |
|
Definition
-hypochromic, microcytic RBCs
-slight anemia that can be misdiagnosed initially as iron deficiency |
|
|
Term
| A person with B-thalassemia major may present with prominent cheek bones and a protrusion of the upper jaw as a result of what? |
|
Definition
| -expansion of marrow cavity in bones of skull and face |
|
|
Term
| In simple B-thalassemia, the production of what is impaired? |
|
Definition
-the production of B-globin alone has been impaired
-almost every type of mutation known to reduce the synthesis of B-globin mRNA or protein has been identified as a cause of B-thalassemia |
|
|
Term
| What is the most common cause of complex thalassemias? |
|
Definition
| large deletions in which the B-globin gene, as well as one or more of the other genes (or LCR) in the B-globin cluster, is removed |
|
|
Term
| What is the cause of Hereditary Persistence of Fetal Hgb (HPFH)? Is this classified as a thalassemia? |
|
Definition
-persistence of gamma-globin gene expression throughout adult life, which is caused by deletions within the b-globin cluster
-NOT a thalassemia |
|
|
Term
| Since patients with HPFH function just fine with gamma globin instead of beta globin, what is a suggested treatment for patients with sickle cell anemia? |
|
Definition
| the concept that turning on the fetal hemoglobin gene in people with sickle cell can help treat them (since sickle cell is caused by a missense mutation in the b-globin gene) |
|
|
Term
| Glucose-6-Phosphate dehydrogenase (G6PD) deficiency is what type of mutation on the G6PD gene? |
|
Definition
|
|
Term
| What does the G6PD enzyme process? What does this processing result in the production of? |
|
Definition
-processes glucose which results in the production of NADPH
-NADPH protects RBCs from the harmful effects of reactive oxygen species |
|
|
Term
G6PD deficiency produces no symptoms until the patient is exposed to what?
G6PD eventually causes what type of anemia? |
|
Definition
environmental factors that increase oxidant stress (e.g. infectious agents, certain drugs and foods, severe stress)
-hemolytic anemia |
|
|
Term
| G6PD deficiency affects 1 in ______ African-american males |
|
Definition
|
|
Term
| in G6PD deficiency, ________/________ are precipitates of the denatured hgb in their cells. Macrophages come along and turn them into ________ cells. |
|
Definition
heinz bodies
bite (premature or inappropriate lysis of our RBCs) |
|
|
Term
| What is the most common cause of anemia? |
|
Definition
|
|
Term
Iron deficiency is caused mainly by ________/_______ in developing countries.
In the US it's main cause is ________/_________ |
|
Definition
-nutritional deficiency
-blood loss (ulcers, colon cancer, hemorrhoids, menorrhagia) |
|
|
Term
| In iron deficiency anemia, what leads to insufficient hgb synthesis? |
|
Definition
| inadequate inatke (or loss) of iron |
|
|
Term
| Describe the RBCs of an iron deficient anemic patient |
|
Definition
| hypocrhomic and microcytic |
|
|
Term
| Iron deficiency anemics are asymptomatic in most cases, but what are 3 symptoms of severe cases? |
|
Definition
weakness
listlessness
pallor |
|
|
Term
What is the most common anemia in hospitalized patients?
It is caused by production of inflammatory __________ associated with what three disorders? |
|
Definition
-anemia of chronic disease
-cytokines: chronic microbial infections, chronic immune disorders, neoplasms |
|
|
Term
| What is the function of cytokines? |
|
Definition
| cause iron to be sequestered in macrophages |
|
|
Term
What are the outcomes of anemia of chronic disease:
increased storage of iron in the _______/________. High serum ________ and serum ________ levels. Reduced total _______-_________ capacity |
|
Definition
bone marrow
ferritin
iron
iron-binding |
|
|
Term
| Megaloblastic anemia is caused by vitamin ________ or ________ deficiency which causes inadequate synthesis of ___________ and defective __________/_________ |
|
Definition
B12 or folate
thymidine
DNA replication (occurs more slowly) |
|
|
Term
Enlarged ___________ precursors in the bone marrow give rise to enlarged __________.
Enlarged __________ precursors give rise to ___________ neutrophils |
|
Definition
hematopoietic (megaloblasts)
RBCs (macrocytes)
granulocytes (giant metamyelocytes)
hypersegmented |
|
|
Term
Megaloblastic anemia causes ___________ hematopoiesis
What are two symptoms of it? |
|
Definition
ineffective
pallor and easy fatigability |
|
|
Term
| What causes aplastic anemia? |
|
Definition
| Bone marrow failure and pancytopenia caused by suppression of mutipotent myeloid stem cells |
|
|
Term
| Half of the cases of aplastic anemia are idiopathic. What are the remaining half caused by? |
|
Definition
| exposure to myelotoxic agents (ex: toxins, radiation, hypersensitivity to drugs or viruses) |
|
|
Term
What happens to the bone marrow in aplastic anemia? What may be the reason for this bone marrow failure?
What are three outcomes from this bone marrow failure? |
|
Definition
-bone marrow becomes hypo cellular with fat replacement
-autoreactive T cells may be the reason for bone marrow failure
-anemia, thrombocytopenia, and neutropenia |
|
|
Term
| Aplastic anemia can be characterized by what 4 symptoms? |
|
Definition
-slowly progressive
-weakness
-pallor
-dyspnea |
|
|
Term
| Define polycythemia (erythrocytosis). |
|
Definition
| the result of an abnormal increase in RBC number |
|
|
Term
| What is primary polycythemia (polycythemia vera):What is it due to? What does it cause? |
|
Definition
-clonal proliferation of myeloid stem cells
-uncontrolled production of RBCs and an increased total RBC mass |
|
|
Term
| What is secondary polycythemia: what is it due to? what is it usually caused by? |
|
Definition
-increased RBC volume owing to erythroid bone marrow hyperplasia caused by erythropoietin
-usually caused by prolong hypoxia (living at high altitudes, anoxia secondary to chronic lung disease, congenital heart disease, renal carcinoma) |
|
|
Term
| Polycythemia vera usually develops late in adult hood. It is caused by what type of mutation in what gene? What does this mutation result in? |
|
Definition
somatic mutation in JANUS KINASE 2 (JAK2)
-this results in constitutive activation of the protein and uncontrolled myeloid cell production |
|
|
Term
| What are some symptoms of polycythemia vera? |
|
Definition
-hypertension
-dark red or flushed face
-headaches
-visual problems
-neurologic symptoms
-splenomegaly
-hypercellular bone marrow |
|
|
Term
| people with polycythemia vera have in increased risk of what 4 things? |
|
Definition
-DVT
-heart attack
-stroke
-leukemia |
|
|
Term
| is polycythemia vera genetic? |
|
Definition
| No, its caused by a somatic mutation |
|
|
Term
| Define leukopenia and leukocytosis. Are they benign or malignant leukocytic disorders? |
|
Definition
-Leukopenia= WBC count below normal
-Leukocytosis= WBC count above normal
-They are benign leukocytic disorders |
|
|
Term
| What do leukemia and lymphoma arise from? Are these benign or malignant leukocytic disorders? |
|
Definition
-leukemia= malignant diseases involving WBC precursors in bone marrow, in peripheral blood (acute and chronic). Lymphoid and Myeloid stem cells
-Lymphoma= lymphoid cell malignant diseases predominantly involving the lymph nodes. arise from WBC in lymph nodes (non-hodgkin's and hodgkin's)
-they are malignant |
|
|
Term
| What causes multiple myeloma? |
|
Definition
| Malignant plasma cells arising in the bone marrow |
|
|
Term
|
Definition
| any substance that is toxic to WBCs, including various drugs |
|
|
Term
| What does leukocytosis occur in response to? |
|
Definition
| bacterial infections (neutrophilia), allergies (eosinophilia), or viral infections (lymphocytosis) |
|
|
Term
What are the age groups most affected by these leukemias:
-acute myelogenous (AML)
-chronic myelogenous (CML)
-acute lymphocytic (ALL)
-chronic lymphocytic (CLL) |
|
Definition
-AML- all age groups
-CML- adulthood
-ALL- most common form affects children under 5 yoa
-CLL- a disease of older people |
|
|
Term
| What are the age groups most often affected by Hodgkins and Non-Hodgkins lymphoma? |
|
Definition
-hodgkin's= all ages, but peaks at 25 and 55 yoa
-non-hodgkin's= more common in adults than children |
|
|
Term
| In leukemias the bone marrow is infiltrated with malignant cells, which leads to what three events? |
|
Definition
-clonal expansion of neoplastic stem cells with genetic changes specific to each disease
-failure of maturation
-suppression of normal hematopoiesis |
|
|
Term
| Patients with leukemia have peripheral blood which contains an increased number of what type of cells? |
|
Definition
|
|
Term
| What are three complications often due to leukemia? |
|
Definition
anemia
recurrent infections
uncontrollable bleeding |
|
|
Term
| What is the aim of treatment of leukemias? |
|
Definition
| reduce the leukemic clone to allow reconstitution with progeny of remaining normal stem cells |
|
|
Term
| What is the most common leukemia? What age group does it primarily affect? |
|
Definition
-Acute myelogenous leukemia (AML)
-affects all age groups, but mainly adults and incidence increases with age |
|
|
Term
| AML is characterized as a heterogenous group of neoplastic diseases characterized by clonal proliferation of _____________ in ___________/_________ and entry into blood or other tissues. |
|
Definition
|
|
Term
|
Definition
| by occurrence of at least 20% myeloblasts in bone marrow biopsy |
|
|
Term
| AML makes up _____% of acute leukemias in adults. |
|
Definition
|
|
Term
| Describe the onset of AML. Without treatment how quickly will most patients die? |
|
Definition
abrupt onset
most patients will die in 6 months w/o treatment |
|
|
Term
| What are some treatment options for patients with AML? |
|
Definition
-chemo (induce remission in 60% of pts, but only 15-30% remain disease free for 5 years)
-bone marrow transplant following high dose radiation and chemo (70% three year survival) |
|
|
Term
| What is the median age of diagnosis for chronic myelogenous leukemia (CML) |
|
Definition
| 45-65 yoa, but all can be affected |
|
|
Term
| CML is characterized by clonal expansion of transformed ___________/__________ cells that increases circulating _________ cells capable of differentiating into __________/_______ |
|
Definition
hematopoietic progenitor
myeloid
neutrophilic leukocytes |
|
|
Term
| 95% of patients with CML have a ____________ chromosome. From what does this result? |
|
Definition
Philadelphia chromosome (Ph1)
resulting from a translocation between chromosomes 9 and 22 |
|
|
Term
| Transformation of progenitor cells and CML is caused by expression of what oncogene? |
|
Definition
|
|
Term
| Explain how a philadelphia chromosome comes about. What chromosomes are the BCR gene and the C-ABL gene located? |
|
Definition
-double stranded DNA breaks occur in the BCR gene on Chr 9 and the C-ABL gene on Chr 22
-translocation occurs between these two chromosomes
-the 22/9 translocation chromosome (Ph1) contains a hybird BCR/C-ABL gene
-expression of this gene causes unregulated cell growth and CML |
|
|
Term
| What does the BCR-ABL gene do that causes CML? |
|
Definition
-it phosphorylates cytoplasmic proteins that control cell growth and differentiation
-this unregulated activation of these signaling pathways results in proliferation of the hematopoietic stem cells, release of immature cells from the bone marrow, and eventually CML |
|
|
Term
| What is the designer drug for CML and what does it do? |
|
Definition
-Imatinib mesylate (Gleevec)
-inactivates the BCR-ABL protein; cancer cells stop dividing |
|
|
Term
| There are three phases to CML: chronic, accelerated, and blast crisis. What are some characteristic features of the chronic phase and the blast crisis? |
|
Definition
-Chronic=insidious onset with development of fatigue, malaise, weight loss, and minimal to moderate splenic enlargement.
-Blast crisis= blasts can be myeloid, lymphoid, erythroid or undifferentiated. Blast crisis is rapidly fatal
*Untreated,the rate of progression from chronic to blast crisis is 5-10% in first two years, and 20% per year after that |
|
|
Term
| Is there an inheritance risk with CML? |
|
Definition
| NO- bc it arises from a somatic mutations that is not found in the germ line |
|
|
Term
| What is the first line of defense for CML? What is the only known curative therapy? |
|
Definition
-Imatinib mesylate (Gleevec)
-allogenic bone marrow transplantation |
|
|
Term
| What is characteristic of Acute Lymphocytic Leukemia (ALL): the bone marrow becomes massively infiltrated with what type of cell? What are some rapid onset signs and symptoms? |
|
Definition
-Massive infiltration of bone marrow with immature lymphoid cells (lymphoblasts)
-Rapid onset with recurrent infections, generalized weakness, and bleeding into the skin and major organs
**lymph nodes are enlarged and mild splenomegaly |
|
|
Term
| ALL constitutes what percentage of childhood leukemias? What percentage of acute leukemias? |
|
Definition
80% (peak incidence is 4 yoa)
30% |
|
|
Term
| In ALL, prognosis in ______-____ cell tumors is predicted by __________ |
|
Definition
|
|
Term
| What is the prognosis for patients with ALL? |
|
Definition
-w/o chemo it is lethal within 3-6 months
-w/ chemo remission can be induced in almost all patients and over 70% can be cured |
|
|
Term
| What is a defining characteristic of chronic lymphocytic leukemia that has to do with the cells? |
|
Definition
CLL cells are indistinguishable from normal mature lymphocytes
-CLL should be suspected if the number of lymphocytes in the blood exceeds 5000/mcL |
|
|
Term
| What are some signs and symptoms of CLL? |
|
Definition
-it a slowly progressive dx with variable phenotype
-many have peripheral lymphocytosis or lymph node enlargement, otherwise asymptomatic
-others with reduced resistance to infections |
|
|
Term
| Who does CLL usually effect and what is the prognosis? |
|
Definition
-most patients are >50 yoa
-most survive 7-9 years from time of diagnosis |
|
|
Term
| Most lymphomas have a ____-cell phenotype |
|
Definition
|
|
Term
| Symptoms of Non-Hodgkin's lymphoma (NHL) are variable, but what are 3 of the most relevant symptoms and clinical findings? |
|
Definition
-Lymph node enlargement: typically painless, may be solitary or diffuse; may be associated with splenomegaly, lymphocytosis, or lymphocytic leukemia
-Systemic constitutional symptoms: fatigue, malaise, fever, weight loss, pruritus, sweating; anemia, leukopenia, infections; autoimmune phenomena
-Extranodal tumor spread= tumor cells infiltrate and compress major organs (e.g., brain) |
|
|
Term
| Hodgkin's lymphoma is pathologically distinct from other lymphomas. It affects all age groups, but who mostly? What types of cells are present in all subtypes of Hodgkin's lymphoma? |
|
Definition
-bimodal with peaks at 25 and 55 yoa
-Reed Sternberg Cells: bilobed or multilobed nucleus and PROMINENT NUCLEOLI surrounded by a clear halo |
|
|
Term
| What are some distinguishable characteristics of Hodgkin's lymphoma: what is characteristic of the lymph nodes? Is there extranodal involvement or leukemic spread? |
|
Definition
-lymph nodes are enlarged (neck and mediastinum)
-Extranodal involvement and leukemic spread are RARE |
|
|
Term
| What the prognosis for Hodgkin's lymphoma? |
|
Definition
-depends on the clinical stage
-stage 1 and 2 tumors are associated with excellent prognosis and a high rate of cute (>90%) with chemo
-advanced disease has less favorable prognosis |
|
|
Term
| Multiple myeloma is a malignant disease of _______ cells. Most patients are older than _____ yoa |
|
Definition
|
|
Term
| The malignant transformation of a single plasma cell in multiple myeloma leads to what happening int he bone? |
|
Definition
| the cell proliferates in the bone marrow and destroys the surround bone (fractures) |
|
|
Term
| What is characteristic of the bones of a person with multiple myeloma? |
|
Definition
| -punched out holes (lytic lesions) in blood forming bones (calvaria and vertebrae) |
|
|
Term
| What are 4 side effects of multiple myeloma? Which of these is the most common cause of death? |
|
Definition
-hypercalcemia
-renal failure (most common cause of death)
-anemia
-leukopenia |
|
|
Term
| What are 4 ways the diagnosis of multiple myeloma can be made? |
|
Definition
-X rays showing lytic lesions
-Serum electrophoresis show monoclonal spike
-bone marrow biopsy shown neoplastic plasma cells in increased numbers
-Bence-Joes proteins in urine |
|
|
Term
| Is chemotherapy effective for patients with multiple myeloma? |
|
Definition
-no
-prognosis is poor
-most patients dies within 3-4 years, primarily of kidney failure or infection |
|
|
Term
|
Definition
escape of blood from the vessels or the heart
-it can be internal or external |
|
|
Term
| Bleeding disorders occur as a result of defects that are related either of what three things? |
|
Definition
-vessel wall related
-platelet related
-clotting factor related |
|
|
Term
| Vascular disorders can be due to what three things? |
|
Definition
-mechanical trauma (injuries)
-vessel wall weakness (cushing's, congenital disorders of CT, scurvy)
-immune injury (vasculitis) |
|
|
Term
| Platelet disorders can be caused by what five different abnormalities? |
|
Definition
-Decreased production of platelets
-increased intravascular destruction of platelets
-increased removal of platelets by spleen
-increased consumption of platelets
-disorders of platelet function |
|
|
Term
| What 4 things can cause decreased production of platelets? |
|
Definition
-aplastic anemia (reduced amount of all hematopoietic cells)
-leukemia
-drugs
-infectious agents |
|
|
Term
| what 4 things can cause increased intravascular destruction of platelets? |
|
Definition
-SLE
-various forms of hemolytic anemias
-drug-induced hematologic disorders
-idiopathic thrombocytopenic purpura (ITP) |
|
|
Term
| What two things can cause increased removal of platelets by the spleen? |
|
Definition
-platelets coated or damaged by antibodies
-hypersplenism (prematurely killing and removing RBCs and platelets) |
|
|
Term
| What causes increased consumption of platelets? |
|
Definition
| disseminated intravascular coagulation (DIC) |
|
|
Term
| WHat two types of disorders cause disorders of platelet function (give an example of each) |
|
Definition
-Congenital disorders (thrombasthenia)
-acquired disorders (chronic renal failure) |
|
|
Term
| What is an example of a congenital clotting factor defect? |
|
Definition
|
|
Term
| What are 3 examples of acquired clotting factor deficiencies? |
|
Definition
-inadequate production of clotting factors
-excessive consumption of clotting factors
-action of anticoagulants |
|
|
Term
| What is the most common heritable bleeding disorder? |
|
Definition
|
|
Term
| What are some signs and symptoms of von willebrand disease? |
|
Definition
-bruising
-nosebleeds
-prolonged bleeding or oozing following an injury
-menorrhagia in women |
|
|
Term
| von willebrand disease is caused by a mutation in what gene? |
|
Definition
| the VWF gene, which encodes the blood clotting protein called von willebrand factor |
|
|
Term
| What is the normal function of VWF gene? |
|
Definition
| to facilitate adhesion of platelets to damaged blood vessel walls, which is an early event in clot formation |
|
|
Term
| What do mutations in VWF cause? what is VWF a carrier for? |
|
Definition
-slow blood clotting and cause prolonged bleeding episodes
-carrier for factor VIII |
|
|
Term
| von Willebrand disease is divided into three types, describe types 1, 2, and 3 |
|
Definition
type 1: reduced amounts of vWF (autosomal dominant, most common, symptoms depend on level of vWF)
type2: altered function of vWF (autosomal recessive, symptoms depend on extent of change in vWF)
type 3: nonfunction vWF (autosomal recessive, rarest, most severe bleeding episodes) |
|
|
Term
| Hemophilia A is what type of genetic disorder? |
|
Definition
|
|
Term
| Hemophilia A is caused by mutation of what gene? |
|
Definition
|
|
Term
| What do mutations of F8 gene cause? |
|
Definition
| deficiency or dysfunction of clotting factor VIII |
|
|
Term
| What are some signs and symptoms of hemophilia A |
|
Definition
| bleeding into soft tissues, muscles, and weight bearing joints |
|
|
Term
| what is the standard of care for hemophilia A? |
|
Definition
| IV replacement of the deficient factor |
|
|
Term
| What type of genetic disorder is Hemophilia B? it is caused by a mutation on what gene? |
|
Definition
x linked recessive
F9 gene |
|
|
Term
| mutations on F9 cause deficiency and dysfunction of clotting factor ______ |
|
Definition
|
|
Term
| What is factor IX leyden? |
|
Definition
| an unusual variant caused by a point mutation in the F9 promotor; causes low levels of factor IX and severe hemophilia in childhood, but spontaneous resolution at puberty as factor IX levels nearly normalize |
|
|
Term
| what is the standard of care for hemophilia B? |
|
Definition
| IV replacement of the deficient factor |
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