HemOnc 01
Terms
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- hematocrit
- volume of blood which is occupied by the RBCs
- RBC lifespan
- 120 days
- Granulocyte lifespan
- 8 hours
- Lymphocyte lifespan
- up to 8 years
- Platelet lifespan
- 7-10 days
-
order the following by INC lifespan
- Granylocyte, Lymphocyte, Platelet, RBC - Granulocyte < Platelet < RBC < Lymphocyte
- is anemia a part of "normal aging"?
- NO
- platelets fxn
- involved with clotting and hemostasis
- in the fetus what are the first detectable sites of blood formation?
- blood islands of the yolk sac
- when during gestation does hematopoiesis in the liver begin?
- 6 weeks, goes until 9 months
- at what stage of gestation does the bone marrow begin to produce blood cells?
- by 24 weeks
- stem cell theory
- immature, self-renewing pleuripotent stem cells arise in early embryogenesis and are responsible for the continuous production of blood cells throughtout life
- from where are diagnostic bone marrow samples usually obtained?
- posterior iliac crest portion of the pelvis
- Burkitt's Lymphoma -- which genetic abnormality?
- 8:14 translocation
- T/F Human hematopoietic stem cells circulate in the peripheral blood as well as in the bone marrow.
- T
- T/F Mast cells are related in lineage to basophils.
- T, despite popular belief (and our syllabus)
- T/F Mast cells express the c-kit proto-oncogene.
- T
- During hematopoiesis, an erythrocyte precursor form that enters the blood and is a useful marker for estimating RBC production rate is the . . .
- reticulocyte
- in normal bone marrow, the most frequent cell type is the . . .
- segmented neutrophil
- the large cell with the multilobed nucleus that gives rise to the platelets is the . . .
- megakaryocyte
- in most patients, bone marrow for diagnostic evaluation is obtained from the . . .
- posterior iliac crest
- the most important chemical factor in the regulation of erythropoiesis is . . .
- EPO
- 5 stimuli for INC intestinal absorption of iron
-
(1) dec iron stores
(2) INC hematopoetic activity
(3) anemia
(4) dec blood oxygen content
(5) dec amount inflammation - what does hepcidin do to intestinal iron absorption
-
INC hepcidin --> DEC intestinal iron absorption
DEC hepcidin --> INC intestinal iron absorption - iron is transported in the peripheral blood mainly by . . .
- transferrin
- T/F Iron deficiency in a male always needs to be worked up.
- T
-
? -
? - what is TIBC?
- transferrin
- Anemia of Chronic Disease
-
- impaired iron utilization; it is not that the body does not have Fe, it just can't use the iron which it has
- low Fe, normal to LOW TIBC, normal to high ferritin - Sideroblastic Anemia
-
- another anemia of impaired iron utilization
- diminished heme synth (e.g. lead poisoning), which leads to INC uptake of Fe by normoblast --> toxic --> ineffective erythropoiesis
- High Fe, Low TIBC, High Ferritin - normoblast aka
-
aka erythroblast
a type of red blood cell which still retains a cell nucleus. It is the immediate precursor of a normal erythrocyte. - Thalassemia
- inherited RBC disease; cells are vulnerable to injury and die easily
- does milk have a lot of iron in it?
- NO, it doesn't -- thus iron deficiency can be an issue in breastfeeding infants
- name the pro-inflammatory cytokines and tell what they do
-
TNF-alpha, IL-1, IL-6
endogenous pyrogens that act on the hypothalamus to induce fever and on the liver to induce the production of the acute phase proteins - Fractional Cell Kill Hypothesis
- A given concentration of a drug, applied for a defined period of time, will kill a constant fraction of the cell population, independent of the number of cells
- outline the three phases of cancer drug human trials
-
Phase I: toxicity
Phase II: Does the drug work?
Phase III: Is the drug better than what is currently available? - should you use intramuscular dosing for pain medication?
- NO; intramuscular dosing is painful and erratic in absorption, and should only be done in emergencies and as a last resort
- give two examples of phagocyte-related chemokines
- IL-8, macrophage inflammatory protein-1 (MIF-1)
- opsonins
-
non-specific proteins that coat senescent cells, bacteria, or particles to facilitate their recognition and ingestion by phagocytic cells
major opsonins: IgG, IgM - tuftsin
- surface IgG is partially digested by the RES cells in the spleen; products released as tuftsin --> potent opsonins that coat encapsulated bacteria to facilitate their rapid removal from the circulation
- MBL
-
Mannose Binding Lectin
an opsonin that binds to the repeating mannose sugar arrays common to many bacteria and fungi - what does the phagocyte NADPH oxidase system do?
- The phagocyte NADPH oxidase system generates superoxide anion by transferring e- from NADPH to O2
- which phagocyte enzyme is responsible for the conversion of superoxide to H2O2?
- superoxide dismutase
- respiratory burst
- transient burst of oxygen consumption that accompanies the generation of oxygen-derived compounds about 50-60 sec after the cell comes into contact with opsonized particles or bacteria
- myeloperoxidase
- enzyme for: H2O2 --> HOCl
- where are eosinophils primarily located?
- located in the subepithelium of the respiratory, digestive, and urinary systems
- what is the major effector function of eosinophils?
- degranulation induced by an IgE/antigen complex binding to the cell
- eosinophil granules
- contain proteins that induce the production of oxygen free radicals
- where are basophils found?
- blood stream
- where are mast cells found?
- primarily in mucosal and connective tissues
- what is the primary consequence of mast cell degranulation?
- vasodilation
-
basophils / mast cells
- general - degranulate when bound to IgE/antigen complex --> release heparin, serotonin, histamine, and cytokines
- NK cells principal fxn
- elimination of altered self cells
- NK cells -- how recognize altered self cells?
-
innate --> reduced expression of Class 1 MHC molecules
adaptive --> Fc-mediated binding of specific antibodies - cyclic neutropenia
- rare autosomal dominant disorder caused by cyclic defects in hematopoiesis
- Chediak-Higashi syndrome
-
- autosomal recessive disorder characterized by neutropenia, albinism, cranial and peripheral neuropathy, and a tendency to develop repeated infections
due to abnormal white blood cells - Chronic granulomatous disease
- recurrent bacterial infections with catalase-positive organisms; granulomas may obstruct GU tract; lack of oxygen radical production, poor bacterial killing
- Hyper-IgE syndrome
-
eczema, respiratory infections, coarse facies, osteoporosis
IgE very high, eosinophilia, DEC neutrophil chemotaxis - Leukocyte adhesion deficiency
- recurrent bacterial infections
- Type 1 LAD is due to what?
- lack of neutrophil B2-integrin adhesion molcule CD18
- Type 2 LAD is due to what?
- defect in the generation or transport of guanosine diphosphate-L-fructose
- MPO deficiency
-
Myeloperoxidase deficiency
- myeloperoxidase in eosinophils but not in neutrophils
- dec production of hydrochlorous acid with delayed killing of microorganisms
- often silent, but disseminated fungal infections common in MPO with diabetes - Cobalmin aka
- B12
- what rxns is B12 involved in in synth of THF?
-
Methyl-THF --> THF
Homocysteine --> Methionine
Methylmalonyl CoA --> Succinyl CoA - lack of B12 will lead to the buildup of . . .
- homocysteine and methylmalonic acid
- desc the Absorption / Metabolism of B12
-
Absorption / Metabolism of B12:
- Ingested B12 is bound to R-binders in the stomach
- parietal cells of stomach produce a substance called intrinsic factor (IF)
- in the duodenum, the B12 binds to IF (displacing the R-binder)
- B12/IF complex goes down to the ileum, where it binds to special receptors and is absorbed
- B12 is transported out of the ileal cell bound to transcobalamin II
- in blood B12 is eventually bound to TC I - desc the diagnostic algorithm of the Schilling test
-
1 – give radioactive B12, if all excreted then everything normal
if not normal . . .
2 – give radioactive B12 + IF, if normal excretion then you know there’s a problem with the gastric production of IF
if not normal . . .
3 – give course of antibiotics ïƒ to see if there’s a “downstream†problem (e.g. bacterial overgrowth) - Pernicious Anemia (PA)
-
Autoimmune disease that causes atrophy of the parietal cells of the stomach lack of acid & IF production
Occurs in late middle age, and is classically seen in people of Northern European descent or in African-Americans. - Neurologic Disease in B12 Deficiency
- Cobalmin necessary for the synth of methionine from homocysteine. Methionine is necessary for proper myelination of nerves, classically problems are seen in the dorsal and lateral columns of the spinal cord, given rise to subacute combined degeneration --> vibration and proprioception
- in treating an anemic patient with B12 deficiency, should you transfuse in addition to intramuscular B12 injections?
- NO, may throw the patient into cardiac failure; instead, just wait for patient improvement
-
what syndrome?
– low retic
– high MCV
– hypersegmented polys
– ineffective erythropoiesis
– nuclear/cytoplasmic asynchrony - Megaloblastic Anemia
- compare and contrast the primary (IgM) and secondary (IgG) immune responses
- IgM forms over 10 days to 2 weeks after antigenic exposure; IgG forms within hours to 1-2 days; response can be 100X greater than primary response
- compare the structure of IgM and IgG
-
IgM -- pentamer
IgG -- monomer - IgM / IgG -- fetus?
-
IgM -- made by fetus, can't cross placenta
IgG -- not made by fetus, CAN cross placenta - IgM / IgG -- bind complement?
-
IgM -- YES
IgG -- NO - IgM / IgG -- hemolysis?
-
IgM -- Intravascular
IgG -- Extravascular