Term
|
Definition
| Allows for evaluation of all hematologic disorders. Used to stage and identify lymphoproliferative. |
|
|
Term
| When may a bone marrow exam be used? |
|
Definition
| During a fever of unknown origin as a function of underlying system disease, fungal infections and other infections |
|
|
Term
| Where do storage diseases spread? |
|
Definition
|
|
Term
| Bone marrow structure at birth |
|
Definition
| All bones are filled with active marrow |
|
|
Term
| Bone marrow structure as one ages |
|
Definition
| Marrow space increases out of proportion to need and excess space is filled with fat |
|
|
Term
| How does the fat to marrow ratio change throughout life? |
|
Definition
| Marrow increases in favor of fat throughout life |
|
|
Term
| Describe the bone marrow structure |
|
Definition
| Reticulu network of support. Many nerves in the bone marow located along the ribs of the collagen. Contains vein and artery with sinusoids. High oxygen tension |
|
|
Term
| History of Hematopoisesis 1949 |
|
Definition
| Lead shielding of hemopoietic tissues prevented death from lethal radiation |
|
|
Term
| History of Hematopoisesis 1951 |
|
Definition
| IV infusion of syngenic marow after radiation also prevented death |
|
|
Term
| History of Hematopoisesis 1961 |
|
Definition
| Marrow continued cells capable of giving rise to colonies of cells of hematopoietic lineages in spleen of irradiated hosts. CFU's |
|
|
Term
| History of Hematopoisesis 1963 |
|
Definition
| Existence of multi-potential hematopoietic |
|
|
Term
| PLuripotential stem cell phenotype |
|
Definition
| CD 34+ thyl+ Lin- HLA-DR Rh123dull |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Rhodamine is normally taken up by mitochondria. If the cell is not cycling the uptake is "dull". Cell is cycling then uptake is greatly enhanced. |
|
|
Term
|
Definition
Pluripotential stem cells
Progenito cells
Maturing cells
Cytokines |
|
|
Term
| Pluripotential Stem Cells |
|
Definition
Multi lineage differential potential
-0.5% of total hematopoietic cells and are not morphologically recognizable. Cells that commit to becoming a certain type of cell at some point |
|
|
Term
|
Definition
Next step of pluripotential stem cells
Restricted to single lineage differential potential (not true stem cells)
3% of all hematopoietic cells and are not morphologically recognizable |
|
|
Term
| How can progenitor cells be measured? |
|
Definition
|
|
Term
|
Definition
95% of total cells (not true stem cells)
Amplified by proliferation
Morphologically recognizable
Proliferative sequence complete before full maturity |
|
|
Term
|
Definition
| Glyocproteins generally responsible for cell to cell communication |
|
|
Term
|
Definition
| They stimulate proliferation and differentiation in specific cell lines, working synergistically with colony stimulating factors |
|
|
Term
| What are two major types of compounds that interact with stem cells? |
|
Definition
|
|
Term
|
Definition
| Activates pluripotential cells, lymphoblasts |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Activates B lymphs and stimulates burst forming colonies in erythropoiesis |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Increases inflammatory activity |
|
|
Term
|
Definition
| Supports stem cells and megakaryotes |
|
|
Term
|
Definition
Potent anti-malignant cell agent
Used against CML melanoma and some solid tumors |
|
|
Term
|
Definition
| Effective against auto-immune activities such as MS |
|
|
Term
|
Definition
| Increases production of superoxides in neutrophils |
|
|
Term
|
Definition
|
|
Term
|
Definition
| 20-25 microns in diatmerter. Round/Oval shape. Nucelus takes up 80% of cell with fine chromatin and one or more well defined nuclei. Very blue and ferratin granules may be seen |
|
|
Term
|
Definition
| 16-18um. Nucelus takes up 75% of cell. Golgi visible. Small amounts of glycogen present and possibility of some hemoglobin production visible |
|
|
Term
|
Definition
| 12-15um. Nucleus takes up less than 50% of cell with well defined heterochromatin. Nucleolus not visible. A lot of hemoglobin production |
|
|
Term
| Nuclear cytoplasmic synchrony |
|
Definition
| Mitotic division that occurs simultaneously with hemoglobin production. |
|
|
Term
|
Definition
| 10-15um. Smallest cell of series. Nucleus is pyknotic (shrunken into a mass). approx 80% of hemoglobin. Some polychromatophilia(high number of rbc's because immature rbc's are being released) |
|
|
Term
| Orthochromic normoblast can undergo an expulsion of the nucleus due to what? |
|
Definition
| Triggering by operons activated by the concentration of hemoglobin. |
|
|
Term
| Expulsion of the nucleus from an orthochromic normoblast last how long and results in what? |
|
Definition
| Takes about 10 mins and results in "cell" capable of transporting itself across the membrane |
|
|
Term
| Bone marrow reticulocytes |
|
Definition
| 10-15um. Contain hemoglobin, centrioles, mitochondria, ribosomes and golgi. Remain for about 2 days in marrow where autophagy (intracellular degredation) and ejection of uneeded organelles occurs |
|
|
Term
| Peripheral blood reticulocytes |
|
Definition
| Live for approx 24 hours. Complete synthesis of hemoglobin and pass through the spleen where it eliminates all organelles. Loses membrane resulting in a shape switch from spheroid to biconcave. |
|
|
Term
|
Definition
| Lives for approx 120 days in circulation. 7.5-8.3um. Capable of deformability (to pass through capillaries and react to changes in pH, osmolality, etc) |
|
|
Term
|
Definition
|
|
Term
| Things necessary for erythrocyte development |
|
Definition
Erythropoietin (EPO)
Iron
Oxygen
Nutritional base for amino acids, carbs, lipids and vitamins |
|
|
Term
| What is iron used for in erythrocyte development? |
|
Definition
| Synthesis of hemoglobin, mitochondria and myoglobin |
|
|
Term
| What is erythropoietin used for in erythrocyte development? |
|
Definition
| Commits and regulates the speed of HB synthesis |
|
|
Term
|
Definition
| Glycoprotein hormone necessary for rbc production that is produced in the kidney and liver. |
|
|
Term
| What is the Erythropoietin release mechanism dependent on? |
|
Definition
| Oxygen saturation at the cell level (baroreceptors)(not red cell level) in the kidney |
|
|
Term
| Erythropoietin mode of action |
|
Definition
| Used via surface receptors and intracelllar secondary messengers such as C-AMP. Can also be used synergistically with adrenergic agonists like thyroid hormones |
|
|
Term
|
Definition
Enhances normoblast maturation and proliferative
Shortens medullary transit time |
|
|
Term
| How do cells become macrocytic? |
|
Definition
| Due to missed mitosis due to increased speed of hemoglobin production via erythropoietin |
|
|
Term
| Erythropoietin increased levels can be found in |
|
Definition
Decreased O2 tension due to:
-anemias
-Obstructive lung disease
-abnormal hemoglobins with unusual oxygen affinity |
|
|
Term
| Erythropoietin decreased levels can be found in |
|
Definition
-Kidney disease or atrophy
- Chronic disease
- Hypothroidism |
|
|
Term
| Red cell metabolism membrane is composed of |
|
Definition
| Typical trilaminar structure |
|
|
Term
| Outer layer of red cell membrane |
|
Definition
| Hydrophilic composed of glycolipid, glycoprotein and protein |
|
|
Term
| Middle layer of red cell membrane |
|
Definition
| Hydrophobic composed of protein, cholesterol and phospholipid |
|
|
Term
| Inner layer of red cell membrane |
|
Definition
| Hydrophilic composed of proteins and lipids |
|
|
Term
|
Definition
| Principle protein that makes up sialic acid and gives rbc negative charge |
|
|
Term
|
Definition
| Protein that binds with actin to make microfilament skeleton which controls the biconcave shape that helps protect the rbc from shearing forces |
|
|
Term
| ATP aids in the phosphorylation of spectrin which |
|
Definition
| Mainains deformability balances in the cell |
|
|
Term
| Increased calcium can increase a Rbc's what? |
|
Definition
|
|
Term
| RBC's are freely permeable to what? Relatively impermeable to what? |
|
Definition
Water, anions Cl- and HCO3-
Relatively impermeable to cations which maintains its volume and water homeostasis through the Na/K pump |
|
|
Term
| Sufficient ATP levels are necessary for what? |
|
Definition
|
|
Term
| 90% anaerobic glycolysis is generated via what pathway? |
|
Definition
| Embden Myerhoff glycolytic pathway which generates ATP and NADH+ from NAD+ |
|
|
Term
| 5-10% of anaerobic glycolysis is generated via what pathway? |
|
Definition
| Hexose monophosphate shunt which gets NADPH from NADP+, which together with reduced glutathiamine, is the main defense against oxidative injury |
|
|
Term
| What happens when NADPH and/or reduced glutathiamine is/are inadequate to neutralize intracellular oxidants? |
|
Definition
| Globin denatures and precipitates forming Heinz Bodies |
|
|
Term
|
Definition
| Pick up oxygen in lungs and releases it in tissues with a lower oxygen tension and pick |
|
|
Term
| Hemoglobin (Conjugated globular protein) composition |
|
Definition
| Cradle of 4 globin chains.2 pairs of dissimilar chains- a frame for the protection and transport of the active portion of the molecule (A tetramer of 4 heme molecules) |
|
|
Term
|
Definition
| Protoporphyrin IX with an atom of divalent ferrous iron (Fe2+) attached |
|
|
Term
|
Definition
| A ring of carbon, hydrogen and nitrogen atoms |
|
|
Term
| Each of the 4 heme groups in a hemoglobin molecule is positioned where? |
|
Definition
| In a pocket of the polypeptide chain near the surface of the hemoglobin molecule. |
|
|
Term
| Each heme molecule combines reversibly with what? |
|
Definition
|
|
Term
|
Definition
| Allows for the physical acceptance of the space occupying oxygen, attached to proteins |
|
|
Term
|
Definition
| Ability of the hemoglobin to take up O2 in the lungs and deliver it to sites of low O2 tension throughout the body |
|
|
Term
| Heme synthesis occurs mostly in the what? |
|
Definition
| Mitochondria (Besides for the first and last steps) |
|
|
Term
| Chemical structure of hemoglobin |
|
Definition
| Two alpha-ALA combine to form a pyrrole compound known as porphobolinogen |
|
|
Term
| Hemoglobin Constitutes: Adult or A1 |
|
Definition
| 2 alpha and 2 beta chains |
|
|
Term
| Hemoglobin Constitutes:A2 |
|
Definition
| 2 alpha and 2 sigma chains |
|
|
Term
| Hemoglobin Constitutes:Fetal |
|
Definition
| 2 sigma and 2 gamma chains |
|
|
Term
|
Definition
| Fetal hemoglobin that consist of 4 epsilon chains |
|
|
Term
| Gower 2 (Embryonic hemoglobin) |
|
Definition
| Fetal hemoglobin that consist of 2 alpha chains and 2 epsilon chains |
|
|
Term
|
Definition
| An embryonic hemoglobin hemoglobin that consists of 2 zeta chains and 2 gamma chains |
|
|
Term
|
Definition
| Stays for about a year after birth. 2 alpha and 2 gamma chains. Has 2 forms. One has a 2 gamma 2136 gly and the othe has a 2 gamma 21136 alanine. Requires 4 loci |
|
|
Term
|
Definition
| Major form of hemoglobin that has oxygen bound to heme |
|
|
Term
|
Definition
| 10-20% of carbon dioxide that has bound to the N-terminal amino group of each globin chain. |
|
|
Term
|
Definition
| Reduced form of hemoglobin that has iron in the 3+ state. Is unable to bind oxygen so it is not functional |
|
|
Term
|
Definition
| Variant hemoglobin that has sulfur irreversibly bound to the oxygen site. Can't be used in the body or quantified. |
|
|
Term
|
Definition
| Variant hemoglobin in which hemoglobin molecule is bound to carbon monoxide and has 500 times the normal affinity for hemoglobin. |
|
|
Term
|
Definition
| Active agent to pick up oxygen from lungs and transport it to cells |
|
|
Term
| Age and gender distribution of iron |
|
Definition
Birth- ABout 300mg
Male adult- 2.5-4.0gm
Female adult- 100mg to 400mg |
|
|
Term
| Daily iron intake for male adult |
|
Definition
|
|
Term
| Daily iron intake for female adult |
|
Definition
| 7% absorbed but lower total = 0.5mg basal conditions should equal 13% |
|
|
Term
| Distribution of body iron |
|
Definition
Total body iron= 4gms
Hemoglobin= 2.5 gms
Myoglobin = 0.130 gms
Iron stores = 1.0 gms |
|
|
Term
|
Definition
Ferritin-60%
Hemosiderin-40%
Transferrin-0.35% or 35 mgm |
|
|
Term
| Heme enzyme concentration in the body. Plasma concentration in the body. |
|
Definition
15 mgm for heme enzymes
35 mgm for plasma |
|
|
Term
| How much iron do individuals need on a daily basis? |
|
Definition
1mgm + any special requirements
Infants and adolescents need an extra 1 mgm for growth |
|
|
Term
| How much iron do females at puberty need on a daily basis? |
|
Definition
|
|
Term
| How much iron do normal pregnant women need on a daily basis? |
|
Definition
|
|
Term
| How much iron do lactating females need on a daily basis? |
|
Definition
|
|
Term
| How much iron do menstruating females need on a daily basis? |
|
Definition
|
|
Term
| All individuals lose how much iron a day through the GI tract, urine, skin, etc? |
|
Definition
|
|
Term
| Menstrual loss of iron a day consist of how much iron? |
|
Definition
|
|
Term
| Pregnancy loss of iron consist of losing how much iron a day mostly in the second and third trimesters? |
|
Definition
|
|
Term
| Lactating females lose about how much iron a day? |
|
Definition
|
|
Term
| Infants and children going through puberty lose about how much iron daily? |
|
Definition
| 2mgm daily (Accounts for normal loss) |
|
|
Term
| Recommended daily minimum iron intake is what? |
|
Definition
|
|
Term
| Dietary form of iron is usually what? |
|
Definition
| Ferric which is converted to ferrous via action of gastric acid at pH less than 4.0 in the presence of reducing substances such as ascorbic acid. |
|
|
Term
| Iron is absorbed through what? |
|
Definition
|
|
Term
|
Definition
| Binds to iron and brings it to the bone marrow where it is stored |
|
|
Term
| What are some interferences with the uptake and utilization of iron? |
|
Definition
Gastric acid pH is greater than 4
Loss of Hcl
Dairy products such as milk, cheese, eggs. etc
Loss of transferin
Liver disease
Inadequate amino acids |
|
|
Term
| Nurse cell phenomenon (rhopheocytosis) |
|
Definition
| Formation of vacuoles at a cell surface caused by the assimilation of droplets (some contain iron) into developing red cell |
|
|
Term
| Iron deficiency state caused by low input can result from |
|
Definition
Prematurity- infant demands to postpartum
Infancy
Weight reduction diets
Pregnancy
Old age (light diet) |
|
|
Term
| Iron deficiency state caused by high output can result from |
|
Definition
Gastro-intestinal bleeding
Uterine bleeding
Pregnancy or lactation
Repeated blood donations
Phlebotomies (for diagnostic purposes) |
|
|
Term
| Iron deficienct can also be caused by |
|
Definition
| GI tract bleeding in the adult male and post menopausal women. Also premenopausal woman and children |
|
|
Term
| Traditional definition of iron deficiency |
|
Definition
| No stainable iron in the marrow |
|
|
Term
| Modern definition of iron deficiency |
|
Definition
| Elevated RDW in the absence of any other RBC numberical abnormalities. Occurs just before stainable iron disappears and is usually diagnosed by a decreased ferritin level |
|
|
Term
| What happens as iron becomes more rare in the body? |
|
Definition
Serum iron decrease/TIBC increase
Plasma ferritin decreases
Percent of Fe absorbance increases
Microyctosis occurs
Retics increase slightly
RBC protoporphyrin increases |
|
|
Term
| If iron deficient occurs secondary to bleeding what happens? |
|
Definition
| WBC and platelets increases are possible |
|
|
Term
| Therapy for iron deficiency includes |
|
Definition
| Correcting the underlying cause whether it may be dietary or primary disease. If uncorrectable (surgical loss of small intestine from some other disease), supplementary iron in P.O. or I.M. form is adminstered |
|
|
Term
| Hereditary sideroblastic anemia |
|
Definition
Sex-linked males. Females show some abnormalities.
Elevated serum iron level, increased marrow stores
Hepatosplenomegaly (enlargement of live and spleen)
50% respond to pyrodoxine |
|
|
Term
|
Definition
Low, high, normal MCV, normal MCHC, elevated RDW
Extreme widening of histogram suggestive of a possible dual population
Anisopoikilocytosis (dimorphism, sideroblastic granules, common ringed sideroblasts)
Ineffective erythropoiesis (low retic in PB, erythroid hyperplasia |
|
|
Term
| What is the earliest sign we have of stress in the bone marrow? |
|
Definition
|
|
Term
| Primary sideroblastic anemia |
|
Definition
| Same as refractory anemia with ringed sideroblasts (RARS) |
|
|
Term
| Secondary siderblastic anemia |
|
Definition
Caused by acute or chronic iron intoxication
Suicides or accidental in children
Increased iron uptake with increased iron absorption
Food fadists |
|
|
Term
| Secondary sideroblastic anemia can be caused by |
|
Definition
Bantus of South Africa
Kaschin-Beck Disease
Alcoholics although complicated by other deficiency states such as folate |
|
|
Term
| Secondary sideroblastic anemia can be caused by environmental factors such as |
|
Definition
Use of anti-tubercular drugs that inhibit pyridoxine metabolism
Heavy metal poisoning |
|
|
Term
| Anemic of chronic diseases |
|
Definition
| Not technically iron deficiency but NOT an iron excess state. (Blockage of iron transfer from macrophages) |
|
|
Term
| Main causes of anemia of chronic disease include |
|
Definition
Chronic infections: tuberculosis, lung abscess, subacute endocarditis
Non infection inflammatory diseases: rheumatoid arthritis, systemic lupus erythematosus, arteritis giant cell, tecidual injury |
|
|
Term
| Pathogensis of anemia of chronic disease |
|
Definition
| Non release of iron by the phagocyte system for the circulating transferrins, preventing iron reutilization. Causes cytokine liberation and as cytokine 1 increases, it increases feritin translation in macrophages |
|
|
Term
| Interleukin 1 increase causes |
|
Definition
Macrophage avidity for iron possibly by inducing lactoferrin liberation by neutrophil
Capture of free iron and transfer rapidly to macrophage
Transferrin use by inflammatory cells
Production of GM-CSF |
|
|
Term
| Tumor necrosis factor increases cause |
|
Definition
Act on the cells of the bone marrow stroma liberating interferon B
Inhibit the red cell series colony formation
Patients with carcinoma, rheumatoid arthritis, parasites, viruses or bacterial infections |
|
|
Term
| Hemoglobin (Conjugated globular protein) composition |
|
Definition
| Cradle of 4 globin chains.2 pairs of dissimilar chains- a frame for the protection and transport of the active portion of the molecule (A tetramer of 4 heme molecules) |
|
|
Term
|
Definition
| Protoporphyrin IX with an atom of divalent ferrous iron (Fe2+) attached |
|
|
Term
|
Definition
| A ring of carbon, hydrogen and nitrogen atoms |
|
|
Term
| Each of the 4 heme groups in a hemoglobin molecule is positioned where? |
|
Definition
| In a pocket of the polypeptide chain near the surface of the hemoglobin molecule. |
|
|
Term
| Each heme molecule combines reversibly with what? |
|
Definition
|
|
Term
|
Definition
| Allows for the physical acceptance of the space occupying oxygen, attached to proteins |
|
|
Term
|
Definition
| Ability of the hemoglobin to take up O2 in the lungs and deliver it to sites of low O2 tension throughout the body |
|
|
Term
| Heme synthesis occurs mostly in the what? |
|
Definition
| Mitochondria (Besides for the first and last steps) |
|
|
Term
| Chemical structure of hemoglobin |
|
Definition
| Two alpha-ALA combine to form a pyrrole compound known as porphobolinogen |
|
|
Term
| Hemoglobin Constitutes: Adult or A1 |
|
Definition
| 2 alpha and 2 beta chains |
|
|
Term
| Hemoglobin Constitutes:A2 |
|
Definition
| 2 alpha and 2 sigma chains |
|
|
Term
| Hemoglobin Constitutes:Fetal |
|
Definition
| 2 sigma and 2 gamma chains |
|
|
Term
|
Definition
| Fetal hemoglobin that consist of 4 epsilon chains |
|
|
Term
| Gower 2 (Embryonic hemoglobin) |
|
Definition
| Fetal hemoglobin that consist of 2 alpha chains and 2 epsilon chains |
|
|
Term
|
Definition
| An embryonic hemoglobin hemoglobin that consists of 2 zeta chains and 2 gamma chains |
|
|
Term
|
Definition
| Stays for about a year after birth. 2 alpha and 2 gamma chains. Has 2 forms. One has a 2 gamma 2136 gly and the othe has a 2 gamma 21136 alanine. Requires 4 loci |
|
|
Term
|
Definition
| Major form of hemoglobin that has oxygen bound to heme |
|
|
Term
|
Definition
| 10-20% of carbon dioxide that has bound to the N-terminal amino group of each globin chain. |
|
|
Term
|
Definition
| Reduced form of hemoglobin that has iron in the 3+ state. Is unable to bind oxygen so it is not functional |
|
|
Term
|
Definition
| Variant hemoglobin that has sulfur irreversibly bound to the oxygen site. Can't be used in the body or quantified. |
|
|
Term
|
Definition
| Variant hemoglobin in which hemoglobin molecule is bound to carbon monoxide and has 500 times the normal affinity for hemoglobin. |
|
|
Term
|
Definition
| Active agent to pick up oxygen from lungs and transport it to cells |
|
|
Term
| Age and gender distribution of iron |
|
Definition
Birth- ABout 300mg
Male adult- 2.5-4.0gm
Female adult- 100mg to 400mg |
|
|
Term
| Daily iron intake for male adult |
|
Definition
|
|
Term
| Daily iron intake for female adult |
|
Definition
| 7% absorbed but lower total = 0.5mg basal conditions should equal 13% |
|
|
Term
| Clinical and laboratory findings for the anemia of chronic disease include |
|
Definition
Chronic disease anemia is generally light to moderate
Symptoms masqueraded by the underlying disease anemia except for nonspecific alterations |
|
|
Term
| Anemia of is usually disease |
|
Definition
Normochromic-normocytic in about a third of the cases. Hypochromic microcytic indicating progressive disease potentially
Decreased iron serum level and serum ferritin |
|
|
Term
| Lab findings in chronic inflammation |
|
Definition
Increased acute phase proteins (gamma globulin, C3, haptoglobin,a1-antitrypsin, fibrinogen
Caused by stimulation of interleukin01,TNF and other cytokines liberated by cytokines |
|
|
Term
| Bone marrow exam on a patient with anemia of chronic disease |
|
Definition
| Bone maow structure and cellularity on a biopsy and aspiration are usually normal expect for changes from underlying disease |
|
|
Term
|
Definition
Observed in bone marrow (Decreased hemoglobin rate mandates more mitotic divisions leading to a microcytic hypochromic anemia)
Abnormal hemoglobins, incomplete form result in precipitated hemoglobin/ iron/ globin- siderotic granules, basophilic stippling, retics |
|
|
Term
| Increased cell death in the marrow results in what? |
|
Definition
Increased anemia.
Increased EP produces vicious circle |
|
|
Term
| Peripheral blood for thalassemia |
|
Definition
Impaired cells from marrow die sooner in the peripheral blood
Decreased haptoglobin due to intravascular hemolysis
Enlarged liver/spleen due to overwork |
|
|
Term
|
Definition
Deletion of an alpha chain gene on chromosome 16. alpha 04.
Incompatible with life.
Severe erythroblastosis (HDFN)
Hydrops (fluid buildup in a person) |
|
|
Term
|
Definition
Known as hemoglobin H disease
Hemoglobin of 8-10 g/dL elevated retic count
Hypochromia, microcytes, ovalocytes, basophilic stippling, nucleated RBC's
40-50% Hb H
Heinz bodies present (positive)
Increased oxygen (Barts is not Beta chains (4 gamma chains) |
|
|
Term
| Alpha thal minor (a02 and a+2) |
|
Definition
SLightly reduced HGB with a normal to slightly elevated RBC count at birth
Severe microcytes (60-75fl) |
|
|
Term
| Iron deficiency caused by alpha thal minor features |
|
Definition
| Oval, elliptical, targetting, tear drop, schistocyte, elliptocal, possibly retics and some inclusions |
|
|
Term
|
Definition
Silent carrier of alpha thal
Produces no clinical effects
Found in family studies |
|
|
Term
|
Definition
| Deletion of beta chain gene on chromosome 11 or a mutation in messenger RNA construction. Smaller less hemoglobin. B02 homozygous o b+2 homozygous. Elevated HGB F and A2. Common poik is targetting. Sigs and symptoms are similar to a3 except no H |
|
|
Term
|
Definition
Heterozygous forms of beta thalassemia minor
Hemoglobin of 10.5-13.9 g/dL
Slight elevation of fetal and A2
Microcytes
Asymptomatic unless stress like pregnancy, etc. occurs |
|
|
Term
| HGB test of peripheral blood for patient with B-chain thal |
|
Definition
Major- 2-6g/dL
Minor- 7-9 g/dL
Minima- Norm-Decr |
|
|
Term
| RBC count test of peripheral blood for patient with B-chain thal |
|
Definition
Major- Low
Minor- Low to norm
Minima- Norm |
|
|
Term
| Retic test of peripheral blood for patient with B-chain thal |
|
Definition
Major- High
Minor- High
Minima- Norm |
|
|
Term
| RBC morph of peripheral blood for patient with B-chain thal |
|
Definition
Major- M/H/P
Minor- M/H/P
Minima- M/N to M/H |
|
|
Term
| Inclusions in peripheral blood for patient with B-chain thal |
|
Definition
Major- Heinz
Minor- Heinz bodies |
|
|
Term
| Hemoglobins Lepore and anti-Lepore |
|
Definition
Not a true thalassemia but a fusion mutation of dela and beta genes.
Normal alpha chain formation
Probably due to an unequal crossing over during meiosis |
|
|
Term
| Hemoglboins in hemoglobin Lepore and anti-Lepore |
|
Definition
Normal embryonic and fetal
Inadequate amounts of A2 and A. Excess alpha chains which are unstable
Hemoglobin Lepore normal alpha chains and sigma beta chains
Absence of normal A hemoglobin with an increase in hemoglobin F but little to no A2 and the presence variant of Lepore |
|
|
Term
| Clinically, Hemoglobin Lepore |
|
Definition
| Looks like sigma beta thal When combined with Hb's like S-very serious |
|
|
Term
| Hereditary persistence of fetal hemoglobin (HPFH) |
|
Definition
A failure/absence of the fetal regulatory genes to shut off.
OR
Failure of adult genes to turn on. |
|
|
Term
|
Definition
| Kilobase deletions near the "switch" region that acts as the operon |
|
|
Term
| Heme synthesis disorders: Step 1 |
|
Definition
| There can be a defect in delta-aminolevulinic acid synthase. No known disorders result from this mutation however |
|
|
Term
| Heme synthesis disorders: Step 2 |
|
Definition
| There can be a defect in delta aminolevulinic acid dehydrogenase |
|
|
Term
| Heme synthesis disorders: Step 3a |
|
Definition
Acute intermittent hepatic porphyria. Symptoms include:
Acute porphyria
Swedish type porphyria
Porphyria hepatitis |
|
|
Term
| Abnormalities in Step 3a of heme synthesis can pathophyisologically cause |
|
Definition
| Loss of uroporphyrinogen I synthetase which resukts in a buildip of porphobilinogen and amino levulinic acid. (This can be caused by many medications including aspiriin) |
|
|
Term
| Heme synthesis disorders: Step 3b |
|
Definition
Congenital erythropoietic porphyria. Symptoms include:
Congenital photosensitive porphyria
Gunther's disease
Porphyria erythropoetical
Blotches on skin (low level burns) |
|
|
Term
| Clinical manifestations of abnormalities in step 3b of heme synthesis |
|
Definition
Dermal photosensitivity
Dermatitis |
|
|
Term
| Abnormalities in step 3b of heme synthesis can pathophysiologically cause |
|
Definition
| Loss of uroporphyrinogen III cosynthetase which causes a buildup of uroporphyrin |
|
|
Term
| Heme synthesis disorders: Step 4 |
|
Definition
Porphyria cutanae tarda
Allows no CNS dysfunction
Lesions on exposed areas
or response to trauma
Erythema, vesicles or bullae, scabs and scarring
Areas of pigmentation/depigmentation, hirsuitism and scleroderma-like changes
Coexisting liver disease
Can be inherited or acquired |
|
|
Term
| Heme synthesis disorders: Step 5 |
|
Definition
| Hereditary or benign corpoporphyria |
|
|
Term
| Abnormalities in step 5 of heme synthesis can pathophysiologically cause |
|
Definition
Loss of coproporophyrinogen oxidase
Absence of coproporphyrin, porphobilonogen and delta aminolevulinic acid during remissions |
|
|
Term
| Clinical manifestations of abnormalities in step 5 of heme synthesis |
|
Definition
Acute attacks of abdominal pain and neurologic involvement
Usually precipitated by drugs
Onset childhood to adult
Autosomal dominant-latent |
|
|
Term
| Heme synthesis disorders: Step 7 |
|
Definition
Erythropoietic protoporphyria
Congenital erythropoietic protoporphyria
Hydroa aestivale |
|
|
Term
| Abnormalities in step 7 of heme synthesis can pathophysiologically cause |
|
Definition
| Loss of heme synthesis which causes a buildup of protoporphyria. Inherited or acquired (acquired through heavy metals such as lead) |
|
|
Term
| Clinical manifestations that result from Abnormalities in step 7 of heme synthesis |
|
Definition
| Dermal photosensitivity and solar erythema |
|
|
Term
| Treatment of Erythropoietic protoporphyria |
|
Definition
Removal of potential exposures
Chelating to withdraw lead from blood and tissue
Lead will recycle from bone during anabolism/catabolism |
|
|
Term
| Morphological classification of simple macrocytosis |
|
Definition
MCV 100-105fl
MCHC greater than 30% with reticulocytosis
Experiencing high altitudes
Recovering form sudden blood loss or chronic anemia
Liver disease |
|
|
Term
| Morphological classification of megaloblastic cells |
|
Definition
MCV from normal (80-100) to 115 fl
MCHC greater than 30%
Can be seen in vitamin b12 def, folic acid def or B12 and folate combined def |
|
|
Term
| Vitamin B12 deficiency history Addison |
|
Definition
| Described case of pernicious anemia and noted a group of males with severe terminal anemia with granulocytopenia and thrombocytopenia |
|
|
Term
| Vitamin B12 deficiency history Erhlich |
|
Definition
| Described abnormal RBC precursors |
|
|
Term
| Vitamin B12 deficiency history Castle |
|
Definition
| Necessity for intrinsic factor. Two different factors were needed for treatments |
|
|
Term
| Lack of intrinsic factor causes what? Where can IF be found? |
|
Definition
Lack of IF causes A significant cause of impaired vitamin B12 absorption.
It can be made by parietal cells in stomach, purified from hog's stomach. No storage of IF, it is made and used immediately |
|
|
Term
| Successful treatment of vitamin b12 deficiency as found by Whipple,, Minot and Murphy |
|
Definition
| Eating a mixture of raw liver and Brewer's yeast |
|
|
Term
| Where can extrinsic factor be found? |
|
Definition
| Cyancobalamin in animal tissues. Sythesized readily and can be stored for approx 5 years in humans |
|
|
Term
| What is attached to vitamin b12? |
|
Definition
|
|
Term
| Vitamin B12 is involved in what? |
|
Definition
Co-facotr in the synthesis of thymine.
Involved in the conversion of methyl malonyl coenzyme A to succinyl
It is also a co-enzyme involved in methionine metabolism |
|
|
Term
|
Definition
Animal proteins: meat, poultry fish, dairy
Intrinsic facto: glycoprotein
R-proteins-cobalamin binding proteins stop absorption |
|
|
Term
| B12 is requireed by cells with what type of metabolism? |
|
Definition
Nucleic acid
Such as buccal, vaginal, gastric and GI cells
Also involved in hematpoietic cells and gametes |
|
|
Term
| Megalogblastic anemia caused by |
|
Definition
| Lack of production Castle's intrinsic factor due to pernicious anemia and the prouction of an auto-immune antibody to intrinsic factor |
|
|
Term
| Megaloblastic anemia also caused by biologic competition such as |
|
Definition
Fish tapeworm
Bacterial overgrowth in the small boewl
Impaired absorption in the ileum
PHS therapy for TB |
|
|
Term
| Megaloblastic anemia signs and symptoms |
|
Definition
Slow development
Long time for the utilization of stores
Impaired methine synthase traps H4 folate as N5-methyl which leads to a secondary or artificial deficiency of folic acid. |
|
|
Term
| Leukopenia can arise as a result of a megaloblastic anemia. What does leukopenia entail? |
|
Definition
| False increase in percent lymphocytes due to decrease in absolute neutropenia with hypersegmented polys |
|
|
Term
| What are the three most important features of Vitamin B12 def? |
|
Definition
Oval macrocytes
Hypersegmented polys
Basophilic stippling |
|
|
Term
| How hypersegmented are the polys in folate def? |
|
Definition
|
|
Term
| How hypersegmented are the polys in Vitamin B12 def? |
|
Definition
|
|
Term
| Erythrocyte characteristics for a patient with a megaloblastic anemia |
|
Definition
Decreased hemoglobin
MCV is greater than 110--140fl
MCHC is norm to high
Macro ovalocytes
Basophilic stippling
Decreased retic count |
|
|
Term
| Describe the bone marrow characteristics for a patient with a megaloblastic anemia |
|
Definition
Ineffective erythro-leuko-thrombopoiesis with extreme hypercellularity
megaloblastic transformation
increase in storage iron due to lack of utilization
Lage megakaryocytes |
|
|
Term
| Lab tests to use when dealing with megaloblastic anemia |
|
Definition
| Increased biliribun, serum iron and LD (isoenzymes 1 & 2) due to increased cell death |
|
|
Term
| Tests for B12/intrinsic factor |
|
Definition
Histamine stimulated gastric analysis
Titrate for the quantity of HCl infer synthesis of intrinsic factor
B12 assay-RIA
Schilling test- parts 1,2 and 3 |
|
|
Term
| Give patient radioactive B12 and collect urine sample if <3% is excreted |
|
Definition
| There is poor absorption of B12 or lack of intrinsic factor |
|
|
Term
| Give patient radioactive B12 and collect urine sample if <7% excreted |
|
Definition
| Problem with patient's GI tract |
|
|
Term
| Hemoglobin results for mild and severe megaloblastic anemia |
|
Definition
M- 11.0 g/dL
S- As low as 1.2 g/dL |
|
|
Term
| Bone marrow results for mild and severe megaloblastic anemia |
|
Definition
|
|
Term
| Peripheral blood results for mild and severe megaloblastic anemia |
|
Definition
|
|
Term
| Iron stores results for mild and severe megaloblastic anemia |
|
Definition
M- Norm to increased
S- Norm to increased |
|
|
Term
| Eryth. plasia results for mild and severe megaloblastic anemia |
|
Definition
M- Asynchronous
S- Hyper/ Ineffective |
|
|
Term
| Folate def is required where? Where can it be found? |
|
Definition
In the same cofactor situations as Vitamin B12 def
Can be found in green leafy veggies, liver and nuts |
|
|
Term
|
Definition
| A pteridine base attached to p-aminobenzoic acid and glutamic acid. |
|
|
Term
| Human folic acid is derived from what? |
|
Definition
|
|
Term
| Active form of folic acid? |
|
Definition
|
|
Term
| Folic acid def can arise from what? |
|
Definition
Diet (overcook everything and no veggies/fruits
Alcoholics- May not eat much
Infancy
Poor absorption
Poor storage (cirrhosis and liver disease)
Competition (anti-folate medications bind to folate reductase 1000x more than folate and inhibits the conversion of folate and dihydrofolate into active tetrahydrofolate) |
|
|
Term
| Poor absorption of folic acid is the result of what? |
|
Definition
Resection or by-pass of small intestine
Drug-induced malabsorpotion
Anti-convulsives |
|
|
Term
| Signs and symptoms of folate def |
|
Definition
Shorter time for stores
Development of severe anemia |
|
|
Term
| Peripheral blood elements for a patient with folate def |
|
Definition
Leukopenia and thrombocytopoenia (False increase in %lymphs due to decrease in abs. neutopenia)
Hyperseg polys |
|
|
Term
| Erthyrocytic elements for a patient with folate def |
|
Definition
Decreased hemoglobin (sometimes as decreased as 1 g/dL)
MCV between 110-140fl
MCHC- Norm to high
Macro ovalocytes
Decreased retic count |
|
|
Term
| Bone marrow elements for a patient with folate def |
|
Definition
| Ineffective erythrocyte-leukothrombopoiesis |
|
|
Term
| Lab tests for a patient with folate def |
|
Definition
Increased bilirubin, serum iron, LD (isoenzymes 1&2 NOT AS ELEVATED AS B12)
Folate assay-RIA measures all folates |
|
|
Term
| Treatments for a patient with folate def |
|
Definition
Folate supplements
Can be stopped when levels return to normal if the primary cause is treated. Monitored with a retic response |
|
|
Term
| Why does pernicious anemia arise from folate def? |
|
Definition
| Because there is a primary def of vitamin B12 which gives a secondary def of folic acid because all the folate ends up trapped as N5-methyl-tetrahydrofolate |
|
|
Term
| Why is folic acid important during early pregnancy? |
|
Definition
| Neural tube closes aound 28th day of pregnancy. Incidence of neural tube defects is reduced by a 400ug folic acid supplement/day before contraception and during the first month of pregnancy |
|
|
Term
| Peripheral blood results for a patient with mild and severe folate def |
|
Definition
|
|
Term
| Hgb results for a patient with mild and severe folate def |
|
Definition
M- Below 11.0 g/dL
S- Below 12 g/ dL |
|
|
Term
| RBC results for a patient with mild and severe folate def |
|
Definition
|
|
Term
| Retic results for a patient with mild and severe folate def |
|
Definition
|
|
Term
| RBC morphology results for a patient with mild and severe folate def |
|
Definition
|
|
Term
| Leuk count results for a patient with mild and severe folate def |
|
Definition
M- Decreased or normal
S- Decreased |
|
|
Term
| Platelet count results for a patient with mild and severe folate def |
|
Definition
M- Decreased or norm
S- Decreased |
|
|
Term
| Arreth count results for a patient with mild and severe folate def |
|
Definition
|
|
Term
| B12 assay results results for a patient with mild and severe folate def |
|
Definition
M- Decreased to norm
S- Decreased to norm |
|
|
Term
| Folate assay results for a patient with mild and severe folate def |
|
Definition
M- Decreased
S- Severely decreased |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
Male- 4.6-6.0x10^6uL or 10^12/L
Female-4.0-5.4x10^6uL or 10^12/L |
|
|
Term
| Hgb (Hb) (Protein in blood that carries oxygen) ref range |
|
Definition
Male- 14-18 g/dL
Female- 12-15 g/dL |
|
|
Term
| HCT (Packed cell volume of red blood cells in blood) ref range |
|
Definition
|
|
Term
| MCV (Mean cell volume) ref range |
|
Definition
|
|
Term
| MCH (Avg mass of hemoglobin per cell) ref range |
|
Definition
|
|
Term
| MCHC (Concentration of hemoglobin of packed rbc's) ref range |
|
Definition
|
|
