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151 Cards in this Set

  • Front
  • Back
What is the production of RBCs, granulocytes and monocytes, and platelets called?
Erythropoiesis, myelopoiesis, and thrombopoiesis.
what enzyme is present in the white cells? Do lymphocytes have this enzyme?
Peroxidase; No, lymphocytes don't have this enzyme.
Why is it important to look at the size of the RBC's when assessing them?
Because in conditions like anemia the size will vary.
What is MCV?
Mean corpuscular volume.
What is an important fact about MCV?
It is a mean, so there might be some large and some small RBC's and the MCV could still be normal because it is a mean.
What is a reticulocyte?
A young red blood cell containing a basophilic cytoplasmic network, they become more numerous during the process of active blood regeneration.
What is MCH?
Mean Corpuscular Hemoglobin. It is the hemoglobin content of the average red cell, calculated from the hemoglobin therein and the red cell count, in erythrocyte indices.
What is MCHC?
Mean Corpuscular Hemoglobin Concentration. Hgb/Hct; the average hemoglobin concentration in a given volume of packed red cells, calculated from the hemoglobin therein and the hematocrit, in erythrocyte indices.
What are the characteristics of normal RBCs?
They look like biconcave discs. They are paler in the middle,
What is a macrocyte?
Macrocyte is an enlarged erythrocyte as seen in pernicious anemia.
What is the cause of the presence of macrocytes?
Liver disease, alcoholism, Oval in megaloblastosis.
What the hell is megaloblastosis?
Megaloblastic anemia is an anemia (of macrocytic classification) which results from inhibition of DNA synthesis in red blood cell production.
What are target cells?
An erythrocyte with a dark center surrounded by a light band that again is encircled by a darker ring; it thus resembles a shooting target; such cells appear in target-cell anemias or after splenectomy
What is the cause of the presence of target cell?
Iron deficiency,liver disease, haemoglobinopathies, post splenectomy
What is a stomatocyte and what is cause of its presence?
A red blood cell that exhibits a slit or mouth-shaped pallor rather than a central one on air-dried smears; Liver disease, alcoholism
What is cause of the presence of pencil cells?
Iron deficiency
What is an echinocyte and what is cause of its presence?
It is a crenated RBC; Liver disease, post splenectomy
What is an acanthocyte and what is cause of its presence?
An erythrocyte characterized by multiple spiny cytoplasmic projections, as in acanthocytosis; Liver disease, abetalipo-proteinaemia, renal failure
When is the fragmentation of the RBC's seen?
When we have problems with the valves. As the blood is ejected it is fragmented.
What is the cause of presence of spherocytes?
Hereditary spherocytosis, autoimmune haemolytic anaemia, septicaemia
What is the cause of fragments?
DIC, HUS, TTP (thrombotic thrombocytopnia). Cardiac valves.
What is the cause of elliptocytes?
Hereditary elliptocytosis.
What is the cause of tear drops?
Myelofibrosis.
What is the cause of basket cells?
Oxidative damage such as occurs in G6PD deficiency.
What is the cause of sickle cell?
Sickle Cell Disease.
What is the cause of microcytes?
Iron deficiency, Thalassemia.
What is the mean life span of RBCs?
120 days.
What is the mean life span of platelets?
8-10 days.
What is the mean life span of neutrophils?
2-4 days.
What is the mean life span of monocytes?
Months.
What is the mean life span of lymphocytes?
Months.
Based on the average life spans what can you say with regards to the activity in the bone marrow?
WBC production occurs more often than RBC production.
Describe the site of Hematopoiesis throughout development?
Occurs in the yolk sac first (up to 6 weeks), then it moves to the fetal liver and spleen (up to 6-7 months). After that it moves permanently to the bone marrow...6-7 months-death.
Where does the production of RBC's start from in the beginning?
Primarily starts from a population of stem cells first observed in the dorsal aorta termed AGM region for aorta gonad mesonephros.
What does the bone marrow consist of?
Hematopoietic (red) marrow, and fatty (yellow) marrow.
What type of marrow is present in all bones at birth?
Hematopoietic or Red marrow.
What happens as we grow up?
fatty or yellow marrow replaces red marrow from 5-7 years of age.
Where is the hematopoietic or red marrow located in an adult?
axial skeleton and proximal long bones.
What 2 layers are bones divided into?
Cortical layer and spongy layer.
What layer contains the bone marrow?
The spongy layer.
How many cell types do you see in the bone marrow? What are they?
9; myeloid precursors (for neutrophils, eosinphils, basophils, and monocytes), erythroid precursos, megakaryocytes, lymphocytes, plasma cells, reticuloendothelial cells, fat cells, osteoblasts, osteoclasts.
What is the precurosor of eryrthocytes? What RBC production called?
Erythroblasts. Erythropoiesis.
What does an RBC start as?
A nucleated cell devoid of hemoglobin.
What is the natural progression of erythropoiesis?
Erythroblast-->proerythroblast-->basophilic erythroblast-->polychromatic erythroblast-->pyknotic erythroblast-->erythrocyte.
What is myelopoiesis?
Production of granulocytes and monocytes.
What is the progression of myelopoiesis?
Myeloblast-->promyelocyte-->Myelocyte-->Metamyelocyte-->stab cell-->polymorph.
What are the characteristics of myeloblast?
immature nucleolus, no granulation.
What are the characteristics of promyelocyte?
primary granulation.
What are the characteristics of myelocyte?
secondary granulation, no nucleolus.
What are the characteristics of metamyelocyte?
indentation of nucleolus.
When does a metamyelocyte become a stab cell?
When we get a bend in the nucleus.
What happens in acute myeloid leukemia? AML?
There is a problem, and there is no maturation past the myeloblast...because of the granules the patient can get DIC.
What happens in chronic myeloid leukemia (CML) in terms of maturation?
They have the ability to mature like normal cells, there are therefore leukemic neutrophils.
What do you get in acute leukemia?
You don't see all the cells that are present in the bone marrow in the blood. This means that the differentiation stops at a certain point and there is no progression.
What do the granules look like in basophils?
They are very dark and sometimes cover the whole of the nucleus.
What are the two pools present in myelopoiesis?
mitotic pool and post mitotic pool.
How long is the process of myelopoiesis?
It can take up to 10 days.
What develops into platelets?
Megakaryocytes; the cytoplasm fragments and forms platelets.
What is the size of this megakaryocyte?
It is HUGE!
What is Endomitotic synchronous nuclear replication?
The nucleus keeps on dividing and when it reaches a larger number of nuclei in the cells it becomes more efficient at producing platelets.
What is the process of monocyte development?
Monoblasts--> promonocytes-->monocytes.
What do they do once they are developed?
They invade tissues.
What are macrohpages called in kidney, brain, serosa, lung, liver, skin, spleen, and bone marrow?
Mesangial cells, microglial cells, serosal macrophages, alveolar macrophages, kuppfer cells, Langerhan cells, spleen sinus macrophages, and bone marrow macrophages.
What do lymphocytes develop from?
Lymphoblasts.
What are some characteristics of lymphocytes?
They don't have granulation and are smaller cells with little cytoplasm.
What is the peripheral blood lymphocyte breakdown?
T cells (65%-80%), B cells (5%-15%), Natural Killer cells.
What are the markers for the 3 types of cells?
T cells- CD2 positive.
B cells- CD19, CD20, CD22 positive.
Natural Killer Cells- CD16, CD52 positive.
Where are the majority of T helper cells and cytotoxic T helper cells located?
CD4 helper cells are located in peripheral blood. CD8 cytotoxic cells are located in the Bone marrow.
Where does lymphocyte production predominantly occur?
marrow is the site of "virgin" lymphocyte production. However,most circulating cells are produced in the secondary lymphoid tissue such as lymph nodes, spleen, thymus and lymphoid tissue of the GI and respiratory tract.
What is a myeloma?
It is a cancer of cells derived from hematopoietic tissue of the bone marrow. A plasma tumor cell.
What symptoms are associated with myeloma?
It causes bone pain, destruction of bones, and fractures.
What is the precursor cell for all the cells in the blood?
Pluripotent stem cells.
What does a pluripotent stem cell divide into?
It divides into CMP and CLP...common myeloid progenitor and a common lymphoid progenitor cells.
What do Common Myeloid Progenitor cells divide into?
They divide into Megakaryocyte-Erythroid Progenitor (MEP) and Granulocyte-Monocyte Progenitor (GMP).
What does MEP divide into?
Megakaryocyte progenitor (MKP) and Erythrocyte progenitor (EP).
What does GMP divide into?
Granulocyte progenitors (GP) and monocyte progenitors (MP).
When we do transplants what cells do we use to do a transplant with?
We do it mostly with Hematopoietic Stem Cells (HSC).
What are the markers of HSC cells?
CD34+, CD38-
How many cells are produced after 20 divisions?
10^6.
Are the HSC cells also found in peripheral blood?
Yes!
What increases their number?
Growth factor.
What happens in an abnormal situation?
In an abnormal situation such as fibrosis in the bone marrow, these cells might migrate and start dividing within the spleen or the liver.
What happens after a HSC terminally differentiates?
It dies.
What does stem cells have that holds everything together?
They have got a number of reeptors.
I know, terrible question!
What do adhesion molecules do?
The mediate the attachment of hematopoietic stem cells, leukocytes, and platelets to the ECM, endothelium and each other.
What upregulates adhesion molecules?
IL-1, TNF, INF-gamma, and viral infections.
What processes are adhesion molecules important in?
3:
1) Inflammatory and immune responses.
2) Platelet and leukocyte vessel wall interaction.
3) On tumor cells, mode of spread and tumor localization.
What do selectins do?
Attach leukocytes and platelets to vessel walls.
What do integrins do?
Mediate cell adhesion during migration and signals for growth and development.
What are some other adhesion molecules?
Cadherins, Sundecams, ADAMs.
What are the major hematopoietic growth factors?
Erythropoietin, colony stimulating factor (CSF), and stem cell factor (SCF)
What is the importance of IL-3?
It seems to be a global growth factor in Hematopoiesis.
What is the source of erythropoietin? How big is it? How are it's levels regulated?
Kidney, liver; 34 kd glycoprotein; levels are regulated by a simple feedback mechanism in response to oxygen tension.
When do we use erythropoietin?
In 5 cases:

1) Anemia of chronic renal failure.
2) AIDs
3) Cancer patients receiving chemotherapy
4) Myelodysplastic syndrome (MDS)
5) Autologous blood transfusion.
What is the use of autologous blood transfusion?
You give a guy erythropoietin before his own surgery and you store his blood in a blood bank to be used for the surgery.
What acts as the oxygen sensor in the kidneys?
The peritubular interestitial cells of the outer cortex.
What is the source of the G-CSF?
Stromal cells, endothelial cells, monocytes and macrophages.
What is the function of G-CSF?
Induces the maturation and proliferation of neutrophil progenitors.
Mobilizes the myeloid sten cells into PB.
activates neutrophils and prolongs their life span.
What are the clinical applications of G-CSF?
1. Post chemotherapy
2. After BMT
3. collection of stem cells from PB
4. Kostmann’s syndrome
What is the problem with it's use?
It causes bone pain.
What is Kostmanns syndrome?
Severe infantile agranulocytosis, an inherited disorder of infancy characterized by severe, recurrent infections and neutropenia.
What is thrombopoietin?
Also known as THPO, it is a glycoprotein hormone produced mainly by the liver and the kidney that regulates the production of platelets by the bone marrow. The receptor for it was discovered before the hormone itself was.
What is the receptor for thrombopoietin?
c-mpl receptor.
What is it's activity?
Lineage dominant factor megakaryocyte progenitor cell proliferation, maturationand platelet production. Affects also erythropoiesis and pluripotent stem cell proliferation
What can you tell based on thrombopoietin levels?
They are inversely related to platelet counts.
What is it called when you don't have enough platelets?
Thrombocytopenia.
When would you give thrombopoietin?
Given to increase platelets levels.
What are lymphokines and monokines?
These are glycoproteins released by lymphocytes and monocytes or macrophages. They have influence on hematopoiesis, the immune response, and response to infection and tumor invasion.
What are the two phases that mitosis is divided into?
G1 and G2...cells can choose not to divide by staying in the G0 stage.
What is the cell cycle influenced by?
By cyclins and Cyclin dependent kinases.
Describe interphase?
Lasts at least 12-24 hours in the mammalian tissue. During this period the cell is constantly synthesizing RNA producing protein and growing in size. It can be divided into 4 steps: Gap 0 (G0), Gap 1 (G1), S (synthesis) phase, Gap 2 (G2).
What is produced in the G1 phase?
RNA and protein. There is an important cell cycle control mechanism that ensures that everything is ready for DNA synthesis.
Which one is shorter: mitosis or interphase? How long does it last?
Mitosis. It lasts about 2 hours.
What are the two checkpoints, G1 and G2, controlled by?
2 things:
Cyclin dependent protein kinases that phosphorylate downstream protein targets.

Cyclins which regulate CDK's.
What is Mantle cell lymphoma?
It is a tumor of lymphoid tissue resulting from a translocation (11;14) containing the IGH gene on Ch. 14 and the cyclin D1 gene on Ch. 11.
Why is Mantle Cell lymphoma called what it is called?
Because there is a mantle zone to the lymphocyte.
How do you diagnose it? What is the prognosis?
Only detected by histology; It has a very bad prognosis.
Why is Mantle cell lymphoma called what it is called?
Because there is a mantle zone to the lymphocyte
How do you diagnose it? What is the prognosis?
Only detected by histology; it has a very bad prognosis.
What is an Aurora kinase?
Family of Kinases important in mitosis and meiosis.
What are aurora kinase A, B and C do?
A- Centrosome
B- Centromere
C- Meiosis.
What is a potential therapy that can be done with aurora kinase inhibition?
Cancer therapy.
What happens when cells die off morphologically?
They fragment.
What are some changes that occur prior to cell death?
Cell shrinkage, chromatin condensation, nuclear fragmentation, and DNA cleavage.
What is apoptosis meadiated by?
Caspases.
What is a caspase?
Cysteinyl Aspartate-Specific Proteases
What are the two pathways that caspases are activated?
1) The death receptor pathway.
2) The Mitochondrial pathway.
What is the intrinsic apoptotic pathway?
Through the mitochondria.
What is the extrinsic death pathway?
Through the death receptor.
How does the extrinsic death pathway work?
Fas and TNF receptor are proteins on the cell surface binding to FasL and TNF which results in the fomation of a death inducing complex.
What is Fas also known as?
CD-95.
What is involved in the intrinsic pathway?
Release of cytochrome C which causes the activation of caspases.
What is the release of cytochrome C controlled by?
Bcl-2 family of proteins.
What is the connection between Bcl-2 proteins and cancer?
In many cancers the levels of Bcl-2 is increased and so the cancer cells don't undergo apoptosis.
What is a specific example of a cancer in which Bcl-2 is over expressed?
Follicular lymphoma: there is a 14:18 chromosomal translocation. Here the Bcl-2 gene is translocated from Ch. 14 to Ch. 18 in proximity to the Ig heavy chain locus.
What are some pro-apoptotic proteins in the same family as the Bcl-2?
BAX, and BAK.
What do they do?
They cause the formation of holes in the mitochondria leading to the leaking of cytochrome C.
What is the connection between P53 and BAX?
P53 induces the transcription of BAX after DNA damage.
What is the connection between Bcl-2 and BAX and BAK?
Bcl-2 inhibits BAX and BAK.
What are the functions of the P53 gene?
It is a tumor suppressor gene that has 4 functions:

1) Apoptosis
2) Cell cycle shut down.
3) DNA repair
4) inhibits O2 reactive species acccumulation.
What is the prognosis if P53 is mutated or is lacking in leukemia?
It is associated with a poor prognosis.
What are the 3 major pathways of signal transduction?
1) JAK/STAT
2) MAP Kinase
3) PI3 Kinase
What is common to all three pathways?
They all involve the phosphorylation of tyrosine residues.
What is an example of JAK/STAT kinase?
Type I cytokine receptor.
What does STAT stand for?
Signal Transducer and Activators of Transcription.
What is an important thing to remember regarding JAK?
It is a pseudokinase; The molecule folds upon itself and the pseudokinase inhibits the kinase.
What happens in a mutation that hinders this folding?
The folding doesn't occur, the tyrosine part of the molecule is not inhibited and the JAK is always activated.
What is another example of JAK/STAT receptor?
The erythropoietin receptor.
What is JAK2 mutation?
It is a somatic mutation that doesn't occur in the normal population and is associated with certain types of hematologic disorders.
What disorders?
3:
1) Polycythemia Vera 90%-95%
2) Essential thrombocytopnia 50%-70%
3) Idiopathic Myelofibrosis 40%-50%
What is the difference if you are homozygous or heterozygous for this mutation?
The severity of the disease.