Term
| Why is hematopoiesis necessary? |
|
Definition
| short life span of blood cells => need for continuous replacement |
|
|
Term
|
Definition
| significant reduction in functional red cell mass with consquent reduction in oxygen carrying capacity |
|
|
Term
| What are the 3 causes of anemia? |
|
Definition
1) blood loss
2) reduced RBC production
3) production of abnormal RBCs or precursor cells |
|
|
Term
| What 9 cells are formed by hematopoiesis? |
|
Definition
1) RBCs
2) eosinophils
3) basophils
4) ganulocytes
5) monocytes
6) platelets
7) B cells
8) T cells
9) NK cells |
|
|
Term
| What plays a role in synthesis of mature cells in hematopoiesis? |
|
Definition
| GFs & cell-cell interactions |
|
|
Term
| Where is erythropoietin synthesized? |
|
Definition
proximal tubular cells of kidney
(sm. amount made in liver) |
|
|
Term
| Why is erythropoietin glycosylated? |
|
Definition
| to prolong half life (it is not essential) |
|
|
Term
|
Definition
1) Reulation of proliferation of committed progenitors (CFU-E), maturation of erythroblasts, & release of reticulocytes
2) Synergistic with IL-3 & GM-CSF to expand BFU-E population
3) promote release of maturer reticulocytes into circulation from bone marrow
4) prevent anemia |
|
|
Term
| When will a patient have a rapid increase of erythropoietin? |
|
Definition
|
|
Term
| How does erythropoietin promote maturation of committed progenitors? |
|
Definition
| binds to membrane surface receptor of bone marrow cells |
|
|
Term
| What are myeloid GFs aka? |
|
Definition
| colony-stimulating GFs (CSFs) |
|
|
Term
|
Definition
| glycoproteins that stimulate proliferation & differentiation of several types of hematopoietic precursor cells & enhance the function of mature leukocytes. |
|
|
Term
| What are the 4 human CSFs? |
|
Definition
1) GM-CSF (granulocyte/macrophage)
2) M-CSF (macrophage)
3) G-CSF (granulocyte)
4) IL-3 |
|
|
Term
| What synthesizes GM-CSF & IL-3? |
|
Definition
|
|
Term
| What synthesizes GM-CSF, G-CSF, & M-CSF? |
|
Definition
| monocytes, fibroblasts, & endothelial cells |
|
|
Term
|
Definition
1) stimulate colony formation of most hematopoietic cell lines
2) synergistic with GM-CSF to increase neutrophils, monocytes & eosinosinophils
3) synergistic with erythropoietin to expanf BFU-E compartment & stimulate CFU-E proliferation
4) influence function of eosinophils & basophils |
|
|
Term
|
Definition
1) synergistic with IL-3 to stimulate colony formation & proliferation of granulocytes, monocytes/macrophages, & megakaryocytes
2) synergistic with erythropoietin to promote formation of BFU-E
3) increases phagocytic & cytotoxic potential of mature granulocytes, but reduces motility & clearance from circulation
4) increases cytotoxicity of eosinophils & leukotriene synthesis |
|
|
Term
|
Definition
1) stimulate granulocyte colony formation
2) synergistic with GM-CSF to simulate granulocyte/macrophage colonies & with IL-3 to induce formation ot megakaryocytes
3) induce release of granulocytes from marrow
4) enhance phagocytic & cytotoxic activities of mature granulocytes |
|
|
Term
|
Definition
1) stimulate monocyte/macrophage colony formation alone & synergistically with GM-CSF & IL-3
2) induce synthesis of G-CSF & IL-1
3) enhance production of IFN & TNF
4) enhance function of monocytes & macrophages |
|
|
Term
| How is erythropoietin administered for therapeutic purposes? |
|
Definition
|
|
Term
| How is erythropoietin used clinically? |
|
Definition
1) anemia due to chronic renal failure
2) transfusion-dependent patients undergoing hemodialysis
3) anemia in patients with progressive renal failure (not requiring dialysis)
4) other anemias
5) preop to increase RBCs to allow storage of larger volumes of blood for autologous transfusion |
|
|
Term
| Do I hate learning about hematopoiesis? |
|
Definition
yes!
(i hope someone reads this card, bc its true) |
|
|
Term
| What is the half life of patients on erythropoietin in chronic renal failure for IV administration? |
|
Definition
|
|
Term
| When is peak plasma concentration seen in SC injection of erythropoietin |
|
Definition
|
|
Term
| Why must dose of erythropoietin be titrated? |
|
Definition
| to avoid excessively rapid increase in hematocrit early in therapy or a rise in hematocrit above 36% during maintenance |
|
|
Term
| Why might a patient need iron supplements in addition to erythropoietin? |
|
Definition
| erythropoietin requires adequate iron stores |
|
|
Term
SE
erythropoietin toxicity |
|
Definition
increase of RBC => HTN & thrombotic phenomena
possible mild allergic rxn |
|
|
Term
| How is erythropoietin SE avoided? |
|
Definition
| raising hematocrit slowly & closely monitoring BP |
|
|
Term
| What internal cell singals occur in the kidney to produce more erythropoietin? |
|
Definition
| Gs stimulation -> increase AC -> increase cAMP -> activation of Kinase A -> activation of phosphoproteins -> stimulation of mRNA production of erythropoietin |
|
|
Term
| What are the 4 major areas meyloid GFs (CSFs) are used clinically? |
|
Definition
1) restoration of normal hematopoiesis in patients with malignancies or non-neoplastic diseases that interfere with marrow production
2) reduction in the morbidity of chemotherapy by diminishing duration of severe neutropenia
3) augmentation of host defenses against inf.
4) adjunct role in chemotherapy to improve cytotoxicity against tumor cells & promote cell maturation |
|
|
Term
|
Definition
site of injection: local induration
site of infusion: thrombophlebitis
fever, myalgia, fatigue, rash, GI Sx, bone pain (common, but dose dependent)
pericarditis, pleuritis, pleural effusions, & pulmonary emboli (dose-limiting)
G-CSF associated with: mild/moderate bone pain, vasculitis & worsening of psoriasis
may have ongogenic potential |
|
|
Term
Hematopoietic GFs
[image] |
|
Definition
1) GM-CSF/IL-3
2) Erythropoietin
3) GM-CSF/G-CSF
4) GM-CSF/M-CSF |
|
|
Term
A 60 yo woman presents with stage IV ovarian cancer. The standard of care Tx is cytoreductive surgery followed by administration of systemic chemotherapy.
1st line therapy consists of carboplatin in combination with paclitaxel. The drugs are given via IV infusion. The "madir" occurs b/w days 10-14.
What can be done to mitigate leukopenia & anemia? |
|
Definition
| Administration of one of the CSFs to promote maturation of the progenitive cells. |
|
|
Term
An obese woman of child bearing age with fertility issues presents for couseling. Blood tests show hemoglobin values <130 g/L.
Example questions: Which follow up tests would you order & what are the likely causes of her anemia? How could this anemia be treated? What impact would be had on a developing fetus if left untreated?
What is this case study illustrating (the only actual question answered on card)? |
|
Definition
| It's important to understand the etiology of an anemia before any Tx is delivered or prognosis. |
|
|
Term
| What is the most common cause of nutritional anemia? |
|
Definition
|
|
Term
| What is the characteristic result of severe iron deficiency? |
|
Definition
| microcytic, hypochromic anemia secondary to reduction in synthesis of Hb |
|
|
Term
| Why does iron deficiency have effects besides those on RBCs? |
|
Definition
| Iron is a required group in many other proteins. |
|
|
Term
| Besides its affect of RBCs, what other effects might occur in iron deficiency? |
|
Definition
| altered muscle metabloism independent of the effect on oxygen delivery via blood |
|
|
Term
| What are the 3 causes of iron0deficiency anemia? |
|
Definition
1) inadequate dietary iron
2) blood loss
3) interference with iron absorption |
|
|
Term
| What is the cause of most nutritional iron deficiency in the U.S.? |
|
Definition
blood loss
1) by the GI
2) by the uterus |
|
|
Term
| How is iron found in the body? |
|
Definition
1) in essential iron containing compounds
2) stored (excess) |
|
|
Term
| Where is 70% of the iron in our body found? |
|
Definition
|
|
Term
| What is the storage form of iron? |
|
Definition
|
|
Term
| How much is ferritin found (molecules or aggregates)? |
|
Definition
| either individual molecules or aggregated form |
|
|
Term
| How many atoms of iron can each ferritin molecule bind? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Where is hemosiderin predominately found? |
|
Definition
reticuloendothelial system in liver
(some in muscle) |
|
|
Term
| What is the plasma protein for iron transport? |
|
Definition
|
|
Term
| What regulates sysnthesis of transferrin receptors & ferritin? |
|
Definition
iron supply
1) when high, sysnthesis of transferrin receptors are reduced & ferritin production is increased
2) if low, tranferrin receptors are increased and ferritin production is decreased |
|
|
Term
| Why is dietary intake or realease from body stores the primary determinant of iron content in cells? |
|
Definition
| low body turnover of iron |
|
|
Term
Where does each stage of Fe absorption pathway occur?
[image] |
|
Definition
1) intestinal lumen
2) mucosa
3) blood
4) tissue |
|
|
Term
| What determines iron requirements? |
|
Definition
| Obligatory physiological losses & need for growth |
|
|
Term
| Why do females require more iron/day than males? |
|
Definition
|
|
Term
| When do females need 4x the normal amount of iron/day? |
|
Definition
| last 2 trimesters of pregnancy |
|
|
Term
| When else might a patient need 4x the daily dose of iron? |
|
Definition
| infants (due to rapid growth) |
|
|
Term
| What are the dietary sources of iron? |
|
Definition
Good: organ meats, egg yolk, oyster, certain dried beans & fruit
Poor: dairy, non-green vegetables |
|
|
Term
| What is the most readily bioavailable form of iron? |
|
Definition
| heme iron (but non heme iron is the majority of dietary iron) |
|
|
Term
| What helps the absorption of nonheme iron? |
|
Definition
|
|
Term
| How does ascorbate increase nonheme iron absorption? |
|
Definition
| 1) complexing with iron
2) reducing Fe3+ to Fe2+ |
|
|
Term
| What are the 2 options of iron deficiency Tx? |
|
Definition
1) Oral iron therapy
2) parenteral iron therapy |
|
|
Term
|
Definition
| nausea, epigastric discomfort, abdominal cramps, constipation, diarrhea (dose related) |
|
|
Term
| How are oral iron therapy SE avoided? |
|
Definition
| taking tablets with meals |
|
|
Term
| When might an iron deficient patient recieve parenteral iron therapy? |
|
Definition
1) cannot tolerate or absorb oral iron
2) chronic blood loss
(since iron stores are repleated more rapidly than by oral therapy) |
|
|
Term
| How are Vit B12 & folic acid deficiencies interconnected? |
|
Definition
| Vit B12 is needed for folic acid to work => deficiency of either results in decreased synthesis of methionine & S-adenosylmethionine => interference with protein synthesis & methylation rxns |
|
|
Term
| What does Vit B12 complex with in the stomach in order to be absorbed? |
|
Definition
|
|
Term
| What secretes IF in the stomach? |
|
Definition
|
|
Term
| What plasma protein transports Vit B12? |
|
Definition
|
|
Term
| What happens to excess Vit B12? |
|
Definition
| stored in liver or excreted in urine |
|
|
Term
| What is the source of Vit B12? |
|
Definition
|
|
Term
| Why is Vit B12 deficiency rare? |
|
Definition
| It would take 3-4 yrs to develop b/c of liver storage |
|
|
Term
| What does absorption of folate require? |
|
Definition
| transport & a pteroyl-γ-glutamyl carboxypeptidase associated with intestinal muscoal membranes |
|
|
Term
| Where does most absorption of folate occur? |
|
Definition
|
|
Term
| What form are folates transported to tissus? |
|
Definition
|
|
Term
| How are folates uptaken into cells? |
|
Definition
| receptor mediated endocytosis |
|
|
Term
| What are the sources of folates? |
|
Definition
| almost all foods, esp. green vegetables, liver, yeast, and some fruit (tho cooking can destroy up to 90% of folate content in foods) |
|
|
Term
| What 2 systems are effected by Vit B12 deficiency? |
|
Definition
| hematopoietic and nervous systems |
|
|
Term
| Why is hematopoiesis sensitive to Vit B12 deficiency? |
|
Definition
| due to its high rate of cell turnover which means it requires high reates of DNA synthesis |
|
|
Term
| What does insufficient Vit B12 do to DNA synthesis & eventually cell maturation? |
|
Definition
| results in highly abnormal DNA => inability of maturing cells to complete nuclear divisions (tho cytoplasmal maturation occurs normally) => production morphologically abnormal cells that die during maturation (most profound effect is in producing abnormally large RBCs - megaloblastic anemia) |
|
|
Term
| What causes for Vit B12 deficiencies? |
|
Definition
| malabsorption due to deficiency in IF or in absorption of IF-B12 complex |
|
|
Term
| How is Vit B12 deficiency treated? |
|
Definition
| parenteral injections of Vit B12 (usually lifelong do to incurable syndromes) |
|
|
Term
| How is Vit B12 deficiency diagnosed? |
|
Definition
| serum measurement of Vit B12 &/or methylmalonic acid |
|
|
Term
| What causes folic acid deficiency? |
|
Definition
| inadequate dietary intake |
|
|
Term
| Who often develops folic acid deficiencies? |
|
Definition
Elderly
Poor
Diets lacking vegetables, eggs & meat
Alcoholics & other patients with liver disease |
|
|
Term
| Does megaloblastic anemia differentiate b/w Vit B12 or folate deficiencies? |
|
Definition
|
|
Term
Tx
folic acid deficiencies |
|
Definition
| 1) proper diagonosis so you don't treat for folic acid deficiency when it's more rare Vit B12 deficiency
2) folate therapy |
|
|
Term
| What does folate therapy do in Vit B12 deficiency? |
|
Definition
| relieves the megaloblastic anemia, but doesn't alter neurological defects due to the Vit B12 deficiency |
|
|
Term
| When can Cu deficiency occur (very rare)? |
|
Definition
intestinal bypass surgery, parenteral nutrition, malnourished infants, Zinc overdose
(NOT usually seen in those with hypocupremia) |
|
|
Term
|
Definition
| decrease activity of Cu-dependent enzymes due to decreased Cu transport (NO hematological abnormalities) |
|
|
Term
|
Definition
leukopenia (esp. granulocytopenia)
anemia |
|
|
Term
| When is Cu therapy indicated? |
|
Definition
| with low plasma [Cu], leukopenia & anemia |
|
|
Term
| What is Cu deficiency usually comorbid with? |
|
Definition
| other nutritional deficiencies |
|
|
Term
| Can humans have Cobalt (Co) deficiency? |
|
Definition
|
|
Term
| When is Co therapy beneficial? |
|
Definition
|
|
Term
| What is Co effect on the body? |
|
Definition
| inhibit enzymes in oxidative metabolism => tissue hypoxia => erythropoietin increase |
|
|
Term
| What happens in Co intoxication? |
|
Definition
depress erythropoiesis
in children: cyanoisis, coma, death |
|
|
Term
| When can oral therapy with pyridoxine Vit B6 increase hematopoiesis? |
|
Definition
| hereditary or acquired sideroblastic anemia |
|
|
Term
| What characterizes sideroblastic anemia? |
|
Definition
| impaired Hb synthesis & accumulation of iron in mitochondria of erythroid precursor cells. |
|
|
Term
| What causes hereditary sideroblasic anemia? |
|
Definition
| x-linked recessive trait (variable penetrance & expression) |
|
|
Term
| What causes acquired sideroblastic anemia? |
|
Definition
number of drugs
inflammatory states
neoplastic disorders
preleukemic syndromes |
|
|
Term
| What rare syndromes can be seen due to riboflavin deficiency? |
|
Definition
spontaneous red-cell aplasia
hypoproliferative anemia |
|
|
Term
| When is riboflavin administration reported to be beneficial? |
|
Definition
| correcting red-cell aplasia in patients with protein depletion |
|
|
Term
|
Definition
| anemia effecting RBC precursors |
|
|
