Exam 3 Flashcards

Question

Renal Cell Carcinoma (RCC)

Answer 1

* **MALIGNANT ADULT TUMOR** * Tumors =\> 0.5 cm. * **Highly vascular tumors** * Derived from the renal tubular or collecting duct epithelium * **_Triad of symptoms_** * **Flank pain** * **Painless hematuria** * **Palpable mass** * Most of the time tumors are detected incidentally

Answer 2

* **_Anemia_** = too few RBC/hemoglobin -\> Decreased oxygen carrying capacity (lack of O2) * **_Polycythemia_** = too many RBC/hemoglobin -\> Thrombosis

Answer 3

1. **Amount of hemoglobin in** **blood** 1. Males: 13.8 - 17 g/dL 2. Females: 12 - 15 g/dL 2. **Hematocrit** 1. The fraction or % of blood that is packed with red blood cells ( = RBC/total cells) 1. Note: WBC and platelets form buffy coat

Answer 4

The production of new blood cells * Normally occurs in red bone marrow * Marrow contains stem cells = **hemocytoblasts** * Certain growth factors will stimulate the proliferation and differentiation of hemocytoblasts to either form RBC, WBC or platelets * **Erythropoietin** = growth factor involved in the proliferation and differentiation of erythrocytes (RBC) = Erythropoesis * under certain extreme conditions this can occur in the liver and spleen * Stem cell -\> maturing cell (in bone marrow) -\> lose nucleus -\> Reticulocyte (goes to blood) -\> lose RNA -\> Erythrocyte (Takes 24 hours to lose its RNA and turn to RBC in blood) * RBC remain in circulation for 110 - 120 days before being removed via hemolysis in the spleen * Macrophage in spleen or liver phagocytose the damaged RBC * Globin -\> Amino acid * Heme -\> * Iron recycled * Converted into bilirubin (yellow pig)

Answer 5

1. **_Anemia of blood loss_** 1. Acute or chronic bleeding 2. **_Anemias of diminished erythropoiesis_** 1. Decreased red cell proliferation (cannot make enough RBCs) 3. **_Hemolytic anemia_ (Hallmark = Erythroid hyperplasia and Reticulocytosis)** 1. Increased red cell destruction 1. Two main mechanisms for Hemolysis: 1. Red cell membrane is damaged and the cell bursts in the blood vessel - **_intravascular_** hemolysis (mechanical forces, toxins) 2. Red cells are defective - undergo **_extravascular_** hemolysis by macrophages mainly in the spleen (liver = backup) = outside blood vessels 1. If spleen contains many more RBC and macrophages because they are deformed (ex. sickle cell anemia) and cannot get out = **SPLENOMEGALY** 2. Extravascular hemolysis also causes increased bilirubin in blood **(hyperbilirubinemia)** and it deposits in the tissue **(Jaundice)** and liver -\> high level in bile **-\> Gallstones**

Answer 6

1. **Hereditary Spherocytosis (**RBC's are spherical) 2. **Sickle cell anemia** 3. **Thalassemia**

Answer 7

* **Hemolytic anemia** * Signs: * General anemia = tired, lethargic, pale skin * Specifically Hemolytic anemia = **gallstones, jaundice, splenomegaly, elevated reticulocyte count in blood** (lots of RBC production to make up for the damaged RBCs), **Anemia** (Subclinical to severe) * **GENETIC -\>** **AUTOSOMAL DOMINANT** **TRAIT** * **SHERICALLY SHAPED** and small RBCs * Mutation in any of these proteins: Band 3, Ankyrin, Spectrin * -\>Weakens link between cytoskeleton and bilayer-\> Unsupported areas of lipid bilayer -\> lose more membrane than cytosol -\> decrease in surface to volume ration -\> spherical shape * Hereditary spherocytosis of a hemolytic anemia occurs MAINLY IN THE SPLEEN (**EXTRAVASCULAR**) because it is a deformation * How can you diagnose someone with this? * Peripheral blood smear and look for spherocytes! * Normal Smear = Normochromic (color), Normocytic (size) _Treatment_: **Splenectomy** (Pro: Reduce RBC destruction to correct anemia; Con: risk of infection)

Answer 8

* Hemolytic anemia * **Mutation in** **beta-globin** chain of Hb * Sickle-shaped RBCs * **AUTOSOMAL RECESSIVE TRAIT** * _Sickle cell anemia_ = if baby born with sickle cell anemia, both parents needed to have sickle cell trait * both mutated alleles (No HbA, mostly HbS) * _Sickle cell trait_ = asymptomatic recessive * One normal and one mutated allele = asymptomatic * O2 removed -\> HbS polymerizes -\> reversible sicking * Multiple cycles of sickling -\> extensive membrane damage -\> increased membrane fragility and decreased membrane deformability -\> lead to hemolysis and phagocytosis by macrophages in the spleen and liver -\> **MUCH SHORTER RBC lifespan (20 days)** * **HbF** prevents symptoms from appearing until 5-6 mo old in babies w/disease (where HbF -\> HbA) * Signs/symptoms: Pallor and fatigue, **Jaundice, gallstones, increased reticulocytes, elevated erythropoietin** (Typical of hemolytic anemia) * **VASO-OCCLUSIVE CRISIS** (spontaneous - blocked vasculature due to clotting, common in legs/extremities) - vascular congestion, thrombosis, infarction, bone pain * Commonly caused by Precipitating stimulus or spontaneously, infection, inflammation, dehydration -\> sickling and sticking of sickled cells to endothelium -\> micro-vascular occlusions -\> tissue or organ ischemia, infarction and sudden, severe pain * More often this occurs _in the bones = bone pain_ . Blood flow tends to be slower and sluggish and hemoglobin undergoes progressive deoxygenation and increased sickling -\> results in significant bone pain, and over time, degenerative changes in bone * **AUTOSPLENECTORMY** in children -\> more susceptible to infection * What happens with these children: First develop splenomegaly -\> Autosplenectomy (numerous splenic infarctions secondary to vaso-occlusion) -\> Small remnant spleen (turns to scar tissue) * Functionally asplenic -\> increased risk of infection **_What are the outcome or prognosis for a person with sickle cell anemia?_** * Many chronic complications * better than it use to be with more supportive care * Functionally asplenic -\> risk of infections * Use of antibiotics to prevent (children under 5) or treat infections has improved outcomes

Answer 9

* Hemolytic anemia * **Reduced synthesis of** **beta-globin** chain -\> inadequate HbA formation -\> RBCs have less Hb _or_ Hb aggregation and precipitation -\> membrane damage -\> * Extravascular hemolysis (Small) * Apoptosis of RBC precursors in marrow -\> ineffective erythropoiesis (larger pathway) _RBC Appearance:_ * Small (**microcytic**) and * pale cells (**hypochromic**) * Variation in size and shape * **TARGET-CELL APPEARANCE** (puddling) _How does the body respond?_ * **Splenomegaly, hepatomegaly (big liver), Skeletal abnormalities (Frontal Bossing)** * because of the ineffective erythropoiesis, the reticulocyte count may not be as high as you may expect (cannot make RBC's) * But because of the huge stimulus for erythropoiesis, the blood may also contain normoblasts * **Child will have GROWTH RETARDATION AND CACHEXIA** * due to ineffective erythropoietic precursors consuming lots of nutrients Treatment: * Bone marrow transplant * Blood transfusion throughout life (required for survival) * major problem with blood transfusion = iron overload due to cannot clear iron fast enough * Iron overload prevented by Iron chelators (long term survival) BETA-THALASSEMIA MAJOR VS. MINOR?? * Minor: * Mild microcytic hypochromic anemia * target cells * asymptomatic

Answer 10

* Inadequate nutrients * Iron * Folic acid * Vitamin B12 * Bone marrow failure (aplastic anemia) * Systemic inflammation (anemia of chronic disease) * Bone marrow infiltration by tumor or inflammatory cells (myelophthisic anemia)

Answer 11

* Diminished erythropoiesis. * Elevated erythropoietin (kidneys aren't working) * Low reticulocyte count (cannot make RBC's) * Iron is required to produce Hemoglobin (cannot transport O2) _Signs/symptoms:_ * _General anemia_: fatigue, listlessness, pale (hypochromic), weakness, small cells (microcytic) * _Iron deficiency anemia:_ **THIN AND SPOONING FINGERNAILS** * **CRAVING FOR CLAY/DIRT** * **LOW IRON STORES** * **=** main way to differentiate beta thalassemia minor from iron deficiency anemia Main causes: * Chronic blood loss (GI tract, uterus) * Pregnancy (increased requirement) * dietary insufficiency (Not is US) * Generalized intestinal malabsorption (gastrectomy or celiac disease) * Iron absorption changes based on iron stores: * **Low iron** stores -\> liver makes **less hepcidin** (inhibit iron absorption)-\> **increased iron** absorption * High iron stores -\> liver makes more hepcidin -\> decreased iron absorption

Answer 12

* **Aplastic Anemia** (bone marrow destroyed) * Toxins, radiation, chemotherapy, drugs * -\> Destroy bone marrow * -\> Anemia (low RBC count), leukopenia (Low WBC count), thrombocytopenia (low platelet count) * **Myelophthisis anemia** (Destroy precursor cells...) * Metastatic cancer inflammatory cells * -\> infiltrate bone marrow * -\> Destroy normal hematopoietic cells * -\> Anemia, leukopenia, thrombocytopenia

Answer 13

* **Vitamin B12 or Folic acid deficiency** * Diminished erythropoiesis * Elevated erythropoietin, low reticulocyte count * Erythroid progenitor -\> lacking either folate or B12 -\> Insufficient DNA synthesis and cell division and unimpaired RNA and protein (Hemoglobin) synthesis -\> Macro-ovalocytes or **LARGE SPHERICAL PALE RBCS (megaloblastic anemia)** * _Cell appearance:_ large, no zone of central pallor (spherical) _Clinical signs/symptoms:_ * Inflammation and atrophy of lingual papillae * How can you tell the difference between folic acid deficiency and Vit B12 deficiency? * Measure blood folate and vit B12 levels, determine if any neurological problem -\> Vit B12 deficiency can cause **nerve demyelination in** **spinal** **cord** * **B12** deficiency can cause CNS problems -\> numbness, tingling, unsteady gait * While megaloblastic anemia is reversible, the neurological problems can be irreversible **_Main causes of Folic acid deficiency:_** * Decreased dietary intake * Chronic alcoholism or liver disease (poor diet and decreased hepatic storage of folates) * Increased requirement (pregnancy) * Malabsorption syndrome (celiac disease and tropical sprue) * Drug induced **_Main causes of Vit B12 deficiency:_** * Folate is destroyed by cooking, B12 IS NOT * Stores of folate will last only a few weeks; stores of B12 last for years * B12 deficiency is mainly caused by: * Loss of intrinsic factor = * **PERNICIOUS ANEMIA** (autoimmune disease to parietal cells or intrinsic factor), gastrectomy * Loss of acid and pepsin to release vitamin B12 from its bound form in food * Gastric atrophy or stomach acid reducing drugs * Loss of intrinsic factor - B12 absorption * inflammatory bowel disease, ileal resection

Answer 14

1***_. Based on origin of the tumor cells (Pluripotent stem cell)_*** 1. **_Myeloid stem cell -\> Myeloid neoplasms_** (Some **leukemias**) 1. Erythrocyte 2. Platelet 3. Granulocytes/monocyte 2. **_Lymphoid stem cell -\> Lymphoid neoplasms_** (some **leukemias** and **non-hodgkin and hodgkin lymphoma**) 1. B cells 2. T cells ***_2. Based on location_*** 1. **_Leukemia_** 1. Starts in **bone marrow** (and blood) -\> spread to **lymph nodes** 2. **_Lymphoma_** 1. Starts in **lymph nodes** -\> spread to **blood and bone marrow**

Answer 15

1. **Cell lineage -\> Myeloid or lymphoid** 2. **Rate of development -\> Acute or chronic** 1. How fast they develop certain symptoms Big 4 types of leukemias discussed: 1. Acute myeloid leukemia (AML) 2. Chronic myeloid leukema (CML) 3. Acute lymphoblastic leukemia (ALL) 4. Chronic lymphocytic leukemia (CLL)

Answer 16

* From myeloid immature **"blasts**" -\>Mutations that: stop differentiation, promote uncontrolled proliferation -\> Acute leukemia _Features of Acute leukemias:_ * Large cells and very large nucleus * Nonfuncitonal cells * Rapidly dividing cells (present w/symptoms within weeks) * Rapidly fatal (\< 6 months w/o treatment) _Clinical presentation:_ (replacement of bone marrow by blast cells) * **Anemia** (weakness, fatigue, pale skin) * **Thrombocytopenia** (Bleeding-petechiae-and hypocoagulation) * **leukopenia/neutropenia** (syseptible to infection, fever, ulcers) * Malaise, Fever/night sweats (hypermetabolic activity), bone pain and tenderness (marrow expansion, increased pressure in the medullary space) * **_ADULTS_**

Answer 17

* From **lymphoblasts** _immature_ **"blasts"** -\>Mutations that: stop differentiation, promote uncontrolled proliferation -\> Acute leukemia ***_CHILDREN_*** _Features of Acute leukemias:_ * Large cells and very large nucleus * Nonfuncitonal cells * Rapidly dividing cells (present w/symptoms within weeks) * Rapidly fatal (\< 6 months w/o treatment) _Clinical presentation:_ (replacement of bone marrow by blast cells) * **Anemia** (weakness, fatigue, pale skin) * **Thrombocytopenia** (Bleeding-petechiae-and hypocoagulation) * **leukopenia/neutropenia** (syseptible to infection, fever, ulcers) * Malaise, Fever/night sweats (hypermetabolic activity), bone pain and tenderness (marrow expansion, increased pressure in the medullary space) * Generalize lymphadenopathy **Splenomegaly** * **AKA: PRECURSOR B AND T CELL LYMPHOBLASTIC LEUKEMIA/LYMPHOMA**

Answer 18

* _Chronic leukemia:_ More **_mature_** (but not full mature) -\> mutations that stop differentiation and promote uncontrolled proliferation * **Adults between 25-60** _Features of chronic leukemias:_ * Cells appear normal (more differentiated) and retain some function, but not really functional * More slowly dividing * Can be asymptomatic for years _Clinical Presentation:_ * Asymptomatic or mild symptoms such as fatigue, malaise, weight loss, excessive sweating (not as bad as acute), bleeding episodes (platelet dysfunction) * Abdominal fullness **(ENLARGED SPLEEN)** * Advances through an **accelerated phase and BLAST CRISIS** (resembles acute leukemia) * **_PHILADELPHIA CHROMOSOME_** * **_bcr-abl fusion_ protein gene on chromosome 22** * ****produces a dysregulated tryrosine kinase involved in cell transformation * Drives the proliferation of granulocytic and megakaryocytic progenitors and release of immature cells in blood

Answer 19

* _Chronic leukemia_: More **_mature_** (but not full mature) -\> mutations that stop differentiation and promote uncontrolled proliferation * **_ADULTS OVER 50_** * Cells appear normal and retain some function * More slowly dividing _Clinical presentation:_ * **Asymptomatic** * Mild systemic symptoms: Fatigue (anemia), Malaise, weight loss, anorexia, bleeding episodes (platelet dysfunction), Lymphadenopathy (enlarged lymph nodes) and splenomegaly (enlarged spleen) * Can transform to a higher grade neoplasm * **Prolymphocytic transformation** -\> large cells in peripheral blood * **RICHTER SYNDROME -\> growing massive lymph node -\> resembles diffuse large B cell lymphoma**

Answer 20

* **Hodgkin lymphoma** (aka Hodgkin's disease) * Neoplastic proliferation of an atypical lympoid cell - Reed-sternberg cell * **Non-Hodgkin lymphoma** * Neoplastic proliferation of B-cells, T-cells or rarely histiocytic cells (macrophages and dendritic cells) Recall: Lymphomas: * Start in lymph node (typical) * -\> Spread to spleen, liver and bone marrow (other organs in advanced disease)

Answer 21

Reed-sternberc cells (Hodgkin lymphoma) * -\> Release many cytokines and chemokines * Inflammatory reaction and tissue fibrosis in the affected lymph node * Eosinophilia * Plasmacytosis (plasma cell development) and hypergammaglobinemia * Features of chronic inflammation (fever, anemia) * Leukocytosis (increased marrow production of leukocytes)

Answer 22

* Neoplastic proliferation of atypical lymphoid cells/germinal center B cells * -\> loss of B cells markers * -\> **REED-STERNBERG CELLS (OWL'S EYES)** * **=** release cytokines/chemokies, * eosinophilia, plasmacytosis, * hypergammaglobinemia, * fever, anemia, leukocytosis, night sweats, * **lymphadenopathy**, * starts with enlargment of a single lymph node or group of lympn nodes * **rubbery and firm nodes** * **Patient population:** * **Bimodal age distribution:** * **Peaks = 20 yrs old and 65 yrs old**

Answer 23

* **Neoplastic proliferation/malignant transformation of B and T cells** * Varies tremendously depending on the type of lymphoma and area involvement: * Can be _slow growing_ and waxing/waning over many years or * _highly aggressive_ resulting in death within a few weeks * Rapidly growing mass * Systemic B symptoms (fever, night sweats, weight loss)

Exam 3 Flashcards

(47 cards)