Term
| What species use an alternative (to glycolysis) pathway of energy generation in erythrocytes? |
|
Definition
| Pigs, use a pathway involving inosine |
|
|
Term
| What species have the highest RBC concentration AND circulating RBC lifespan? |
|
Definition
Horses, have around 9 million RBC/ul with a circulating lifespan of 150 days
Cattle have an equally long lifespan but only 7 million RBC/ul |
|
|
Term
| What is the disease process associated with decreased globin synthesis? |
|
Definition
Thalassemia
**vs. a genetic mutation that produces an altered global molecule = hemoglobinopathy (not described in veterinary species) |
|
|
Term
| What state is Fe in hemoglobin? How is this state maintained? |
|
Definition
| Ferrous (Fe+2) i.e. reduced The ferrous state is maintained by methemoglobin reductase and NADPH diaphorase |
|
|
Term
| What state are the amino acids in globin chains and how is this state maintained? |
|
Definition
reduced state (Fe in heme is also in a reduced (+2, ferrous) state)
maintained by glutathione reductase and catalase |
|
|
Term
| How is the majority of CO2 produced in the tissues transported to the lungs (70%)? |
|
Definition
CO2 from tissues is taken up into RBC and converted into H+ and HCO3- via carbonhic anhydrase
Hgb acts as a buffer for released H+
The reaction is reversed when the RBC returns to the lungs and CO2 is released via respiration |
|
|
Term
| How is the remaining 20% of CO2 produced by tissues transmitted to lungs (i.e. the CO2 that isn't transmitted via carbonic anhydrase mediated reactions)? |
|
Definition
| 20% of CO2 from tissues diffuses into RBC and bind stop Hbg to form carbaminohemoglobin which is then transported to the lungs for expiration |
|
|
Term
| What is the major rate limiting enzyme in hemoglobin synthesis? What cofactor is necessary to this enzyme to function? |
|
Definition
5-Aminolevulenic acid synthase
**requires Vit B6 (pyridoxine) as a cofactor |
|
|
Term
| What enzymes involved in hemoglobin synthesis are inhibited by lead? |
|
Definition
5-aminolevulenic acid synthase (rate limiting enzyme)
porphorobilinogen synthase
ferrochelastase
coproporphyrinogen oxidase
**in lead toxicity results in increased concentrations of heme precursors in erythrocytes (aka porphyria) |
|
|
Term
| Which veterinary species do not synthesize fetal hemoglobin? |
|
Definition
dogs, cats, and horses
** embryonal hemoglobin (2 alpha, 2 epsilon globin chains) is replaced by adult hemoglobin (2 alpha, 2 beta globin chains) during fetal development |
|
|
Term
| How to the globin chains vary in type and amount in embryonic, fetal (ruminants only), and adult hemoglobin? |
|
Definition
Embryonic Hgb has mostly 2 alpha, 2 epsilon globin chains
Fetal Hgb has mostly 2 alpha, 2 gamma globin chains
Adult Hgb has mostly 2 alpha, 2 beta globin chains
**Most veterinary species have only embryonal and adult Hgb, ruminants have fetal Hbg and at birth have a mixture of fetal and adult Hbg which transitions to only adult after a few months. |
|
|
Term
| What are the three stages of hemoglobin synthesis? |
|
Definition
a series of porphyrin reactions
incorporation of iron into protoporphyrin IX (catalyzed by ferrochlastase) to form heme
binding of four ferriheme and four globin chains to form hemoglobin |
|
|
Term
| Hemoglobin is degraded into what four substances? |
|
Definition
heme: bilirubin, Fe+2, and CO
globin: amino acids |
|
|
Term
| Other than hemoglobin, what are three other heme containing molecules? |
|
Definition
catalse
peroxidase
cytochromes |
|
|
Term
| How does unconjugated bilirubin enter hepatocytes? |
|
Definition
via receptors of the organic anion transport polypeptide family (OATP)
**bilirubin enters hepatocytes without albumin attached |
|
|
Term
| Where in a hepatocytes is bilirubin conjugated, and what molecule is predominantly used to conjugate bilirubin in most veterinary species? |
|
Definition
Bilirubin conjugation occurs in the endoplasmic reticulum, bilirubin is conjugated with glucuronide in most veterinary species
**horses use glucose to conduct the majority of their bilirubin (> 60%) |
|
|
Term
| What is the primary transporter for excretion of conjugated bilirubin from the hepatocyte into the bile canaliculi? |
|
Definition
Multi drug resistance protein 2 (aka canalicular multi specific organic anion transporter cMOAT)
** this is the rate limiting step in bilirubin excretion and is an energy dependent process |
|
|
Term
| How is total body iron distributed in health? |
|
Definition
50-70% in erythrocyte hemoglobin
23-40% in storage
the remainder in other molecules (e.g. myoglobin, cytochromes and other enzymes) |
|
|
Term
| How does hepcidin affect intestinal absorption and handling of Fe? |
|
Definition
hepcidin decreases intestinal absorption and export of Fe from enterocytes.
Hepcidin binds to membrane ferroportin (normally involved in exporting Fe from cells) causing it to be internalized trapping any absorbed Fe within enterocytes --> accumulation of intracellular Fe inhibits expression of enterocyte surface receptors (divalent metal transporter 1 and duodenal cytochrome b/ferric reductase) involved in absorption of Fe into the enterocyte |
|
|
Term
| How are hepcidin concentrations modulated in enterocytes? |
|
Definition
decreased hepcidin production occurs when hepatocytes detect hypoxia or in iron deficient states
increased hepcidin production occurs with excess Fe (diet, blood transfusions) and inflammation (IL-6 in particular promotes hepcidin production) |
|
|
Term
| What is the circulating lifespan of reticulocytes in non-anemic dogs? |
|
Definition
| 1-2 days (afterwhich the cells develop into mature erythrocytes) |
|
|
Term
| How does the degree of reticulocyte reticulation correspond to age and degree of polychromasia? |
|
Definition
| The more heavily reticulated reticulocytes (type III) are youngest and have the highest degree of polychromasia and are typically larger than the more mature reticulocytes |
|
|
Term
| How long after a stimulus (e.g. hemorrhage or hemolysis) is the maximum concentration of younger (e.g. larger, more reticulated) reticulocytes greatest? How does this compare with the time frame to the maximum concentration of more mature reticulocytes? |
|
Definition
Maximum concentration of more immature reticulocytes (type II, type III) occurs 4 days after the onset of anemia
vs.
Maximum concentration of more mature reticulocytes (Type 1) occurs about 10-12 days after the onset of anemia.
The circulating lifespan of more mature reticulocytes is longer (3 days) compared to the more immature reticulocytes (12h) |
|
|
Term
| What form of Fe is absorbed by enterocytes? |
|
Definition
| Fe+2 (ingested Fe+3 is converted to Fe+2 by doudenal cytochrome b aka ferric reductase) |
|
|
Term
| What other enzyme (other than ferroportin) is involved in movement of Fe from enterocytes into circulation? |
|
Definition
| hephaestin (a copper containing Fe oxidase, related to ceruloplasmin) |
|
|
Term
| How is Fe transported in plasma? |
|
Definition
bound to apotransferin (a beta globulin produced by hepatocytes)
Fe+apotransferin = transferin, which carries Fe+3 to and from tissues |
|
|
Term
| What cells have the highest amount of transferrin receptors? |
|
Definition
marrow erythroid cells
hepatocytes |
|
|
Term
| How does plasma ferritin differ from tissue ferritin? |
|
Definition
Plasma ferritin is a glycosylated polymer that is relatively Fe poor
tissue ferritin is nonglycosylated and relatively Fe rich
*Apoferritin combines with Fe+3 to form ferritin, the storage form of Fe |
|
|
Term
| What is the major storage form of Fe? |
|
Definition
Hemosiderine
a complex of Fe oxides and protein found predominantly in lysosomes of macrophages. Hemosideirn is relatively insoluble and poorly mobile compared to ferritin |
|
|
Term
| What are blood group factors? |
|
Definition
| erythrocyte surface antigens |
|
|
Term
| What is the most common bloody type in dogs in the USA? |
|
Definition
DEA 1.1 (50%)
20% have DEA 1.2 |
|
|
Term
| What blood type in cats lack natural antibodies against any blood-type antigens? |
|
Definition
Type AB
*Type B cats have naturally occurring anti-A antibodies |
|
|
Term
| What blood types in horses are associated with neonatal isoerythrolysis? |
|
Definition
|
|
Term
| Which equine blood types are associated with naturally occurring antibodies? |
|
Definition
horses that lack Aa, Ac, or Ca may have natural antibodies against these antigens.
**this is why plasma donors should be Aa, Ac, and Ca positive |
|
|
Term
| What is the rate limiting enzyme in anaerobic glycolysis in erythrocytes? |
|
Definition
phosphofructokinase
**activity of phosphofructokinase is enhanced by alkalemia and reduced by acidemia |
|
|
Term
| What is the function of the hexose monophosphate shunt (aka pentose shunt aka pentose phosphate pathway) in erythrocytes? |
|
Definition
generation of NADPH that is used to keep glutathione in a reduced state.
** Glutathione and NADPH help maintain Hgb and other proteins in a functional reduced state ** |
|
|
Term
| What is the rate limiting enzyme in the hexose monophosphate shunt (production of NADPH and glutathione to keep Hgb and other proteins in a reduced functional state)? |
|
Definition
| Glucose-6-phosphate dehydrogenase |
|
|
Term
| What is the function of the diphosphoglycerate (DPG) shunt in erythrocytes? |
|
Definition
production of 2,3-DPG (at the expense of ATP production), which decreases O2 affinity of Hgb promoting O2 delivery to tissues
** dogs and horses have high erythrocyte [2,3-DPG], while cats and cows have very little |
|
|
Term
| What species have high concentrations of 2,3-DPG in their erythrocytes? What physiologic effect does this have? |
|
Definition
Dogs and horses have high 2,3-DPG concentrations, this decreases the affinity of Hgb to O2 facilitating O2 delivery to tissues
**cats and cattle have low 2,3-DPG concentrations in their erythrocytes |
|
|
Term
| How can the erythrocyte indices be used to calculated MCHC? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| How is the RDW calculated? |
|
Definition
it's essential the CV of the MCV so,
RDW = (standard deviation of MCV/ MCV) x 100 |
|
|
Term
| What HGB related RBC index is directly measured (ADVIA)? |
|
Definition
CHCM- average cellular [Hbg] determined directly by light scatter
**unaffected by most of the spectral inteferences that can falsely elevated MCHC but can be increased by heinz bodies which alter light scatter |
|
|
Term
| How is CH different from MCH? |
|
Definition
CH is calculated from direct measurements of each RBC [Hgb] (via light scatter, increased high light scatter = increased refractive index = increased [Hgb])
MCH is calculated from [Hgb] measured via cyanmethemoglobin method following RBC lysis, so spectral interferants in the plasma (e.g. free Hgb, lipemia) will more significantly affect MCH than CH |
|
|
Term
| How does the advia distinguish between platelets and erythrocytes? |
|
Definition
refractive index (high light scatter)- PLT have a lower refractive index than RBC
**the ADVIA also uses refractive index to determine the [Hgb] in individual erythrocytes (greater scatter/refractive index = more Hgb) |
|
|
Term
| What dye does the advia use to detect reticulocytes? |
|
Definition
Oxazine 750
*stains cellular RNA which increases light absorption compared to mature RBC, detected by absorbance spectrophotometry |
|
|
Term
| What method does the ADVIA (and all other hematology instruments) use to detect blood [Hgb]? |
|
Definition
cyanmethemoglobin*
*following RBC lysis |
|
|
Term
| How is the [Hgb] estimated by the QBC method? |
|
Definition
The lower the MCHC the less dense the RBC are, the lower the float can sink within the RBC layer
Hgb is calculated mathematically once the RBC density is determined, from this the other RBC indices (MCH, MCHC can be calculated)
MCH= [Hgb]/[RBC], MCHC=[Hgb]/[HCT] |
|
|
Term
| How do blood-gas/POC electrolyte analyzers determine HCT? |
|
Definition
HCT is determined by measuring the electrical conductivity of the blood
**there is an inverse relationship between electrical conductivity and [HCT], that is the electrical conductivity of the blood decreases as the HCT increases. <- PLT and WBC also contribute, but since they are such a small component of blood relative to RBC this is an ok method for determining HCT |
|
|
Term
| How does hypernatremia or hyponatremia affect the calculated HCT? |
|
Definition
When the patient is hypernatremic, the blood (and RBC) are hypertonic compared to the analyzer's diluent fluid --> RBC swell --> falsely increase HCT
When a patient is hyponatremic, the blood (RBC) are hypotonic compared to the analyzer's diluent and the RBC shrink --> falsely decreased HCT |
|
|
Term
| How can marked hyperproteinemia affect calculated HCT using conductivity methodology (e.g. blood gas, electrolyte analyzers)? |
|
Definition
marked hyperproteinemia decreases the conductivity of blood so the calculated HCT Wwill be falsely increased
*conductivity is inversely proportional to HCT |
|
|
Term
| What is the equation for the corrected reticulocyte percentage? |
|
Definition
Reticulocyte (%) x patient HCT/average HCT for species
**If the corrected reticulocyte percentage is <1, then the anemia is non regenerative |
|
|
Term
| What fluorescent dye is used to detect reticulocytes by the Sysmex? |
|
Definition
|
|
Term
| In general, how does reticulocyte maturation time vary with the degree of anemia? |
|
Definition
the more anemic --> greater reticulocyte maturation time
*this makes sense because more younger reticulocytes are release when the anemia is more severe and they take longer to mature into RBC |
|
|
Term
| What type of hemolysis is most commonly associated with ghost cell formation? |
|
Definition
complement mediated intravascular hemolysis
**must be distinguished from smearing trauma, often more distorted if this is the case (i.e. as opposed to true ghost cell formation) |
|
|
Term
| What is the pathogenesis of basophilic stippling associated with lead toxicity? |
|
Definition
| inhibition of pyrimidine 5'- nucleotidase (normally helps degrade nucleotides in RNA) |
|
|
Term
| What are siderotic granules (pappenheimer bodies)? |
|
Definition
iron laden mitochondria
*differentiated from basophilic staining because they tend to be more aggregated and pale staining (basophilic stippling is evenly dispersed and dark staining). Can confirm with Prussian blue |
|
|
Term
| Why is microcytosis associated with iron deficiency? |
|
Definition
| with iron deficiency increased RBC cell divisions occur because cellular [Hgb] is not great enough to inhibit mitosis |
|
|
Term
| In what species do young individuals have microcytic erythrocytes compared to adults? |
|
Definition
| horses (up to 6 months of age) and kittens |
|
|
Term
| What inherited disorders have been associated with eccentrocyte formation in horses? |
|
Definition
G6PD-deficiency (rate limiting enzyme in the pentose phosphate pathway which protects RBC against oxidative damage)
FAD- deficiency (FAD is necessary for normal glutathione reductase activity, reduced glutathione is a potent antioxidant so horses with FAD deficiency have RBC that are prone to oxidative injury and prominent eccentrocytosis) |
|
|
Term
| What inherited disorder has been associated with echinocytes in dogs? |
|
Definition
| pyruvate kinase deficiency (pyruvate kinase is involved in RBC ATP generation via anaerobic glycolysis, pyruvate kinase deficiency results in RBC ATP depletion, shorted RBC lifespan and mild to severe hemolytic anemia) |
|
|
Term
| What hereditary disorders in dogs are associated with canine hereditary ovalocytosis? |
|
Definition
spectrin mutation
protein band 4.1 deficiency |
|
|
Term
| What are some ways to distinguish pyknocytes from spherocytes via light microscopy? |
|
Definition
pyknocytes stain more intensely with new methylene blue than normal RBC or spherocytes.
They often also have some membrane irregularities or tags and are not perfect spheres |
|
|
Term
| What inherited RBC disorders have been associated with spherocytes? |
|
Definition
PK-deficient dogs (ATP depleted RBC are more fragile, typically have mild to severe hemolytic anemia, may also have many echinocytes)
dyserythropoeisis english springer spaniels
Hereditary band 3 deficiency in japanese black cattle |
|
|
Term
| In which dog breed has asymptomatic hereditary stomatocytosis been reported? |
|
Definition
schnauzers (miniature and standard)
pomeranians
Â
**associated with altered RBC cation exchange (increased intra-RBC [Na] and [K] --> RBC swelling. |
|
|
Term
| In which dog breeds has hereditary stomatocytosis been reported in association with other pathology? |
|
Definition
Malamutes (also chondrodystrophic)
Drentse patrijshond (concurrent hypertrophic gastritis) |
|
|
Term
| In which species does peak reticulocytosis, following an EPO stimulation, occur quicker than others? |
|
Definition
| Cats (aggregate retics peak at 4 days post stimulus, punctate retics peak at 9 days and remain above baseline for weeks.) **most other species peak at 7-10 days post stimulus |
|
|
Term
| What comes first with iron deficiency, microcytosis or hypochromasia? |
|
Definition
|
|
Term
| What is the best way to assess wether or not a sample's MCHC is falsely increased (because of hemoglobin or other spectral interferences in the plasma)? |
|
Definition
Compare MCHC to CHCM, if CHCM is normal the MCHC is likely falsely increased
**MCHC is measured chemically after lysis of RBC (so anything in the plasma can potentially affect it) while CHCM is measured spectrophotometrically in intact RBC, only heinz bodies can falsely increase CHCM
if BOTH MCHC and CHCM are increased this implies in vivo cell shrinkage due to hyponatermia in the patient so H20 shifts out of RBC into relatively hyperosmolar analyzer diluent |
|
|
Term
| What is the only true pathologic hyperchromic state? What other change to RBC indices may accompany this state? |
|
Definition
Marked eccentrocytosis and pyknocytosis can result in a hyperchromic state due to loss of RBC volume in excess of Hgb, so that are also usually microcytic (might not be enough to change MCV though).
Rarely, some spherocytic anemias can be associated with loss of RBC volume and may be hyperchromic, but usually spherocytes have a normal MCV despite appearing smaller on blood smears |
|
|
Term
| How do RBC lifespan vary by species? |
|
Definition
| cats have the shortest (70d), dogs middle (100d), horses and cattle have the longest (150d) |
|
|
Term
| How does inflammation affect iron mobilization/utilization by RBC precursors? |
|
Definition
IL-6 stimulates hepcidin production by the liver --> hepcidin binds to membrane ferroportin on macrophages preventing export of Fe following routine Hgb degradation
Apoptransferin is a negative acute phase protein so Fe mobilization is also diminished in inflammatory conditions |
|
|
Term
| What is the expectation for bone marrow stainable Fe in animals (except cats) with anemia of chronic/inflammatory disease? |
|
Definition
Increased to normal Fe
**and also increased to normal serum [ferritin] |
|
|
Term
| What is the pathphysiology of the marked hyperbilirubinemia in cats with cytauxzoon? |
|
Definition
hepatic damage and cholestasis (secondary to the schizonts)
**although there are piroplasms within RBC the anemic is of chronic disease and hemolysis is considered a minor if at all, contributor** |
|
|
Term
| What bone marrow findings are expected with immune-mediated non-regenerative anemia? |
|
Definition
Erythroid hyperplasia (if attacking only at the reticulocyte level)
Left shift and maturation arrest
Aplasia/PRCA (if attacking at the level of the erythropoietic stem cell)
*often erythrophagia of later stage RBC precursors can be at least rarely observed within macrophages |
|
|
Term
| Describe the pathogenesis of anemia associated with copper deficiency in dogs and pigs? |
|
Definition
Copper is a component of two oxidative enzymes, ceruloplasmin (mac) and hephaestin (enterocytes), that convert Fe+3 --> Fe+2 for transport out of the cell and into the plasma.
So, with copper deficiency there is less release of Fe from Hgb degradation by macs (ceruloplasmin) and less release of Fe from dietary absorption (hephaestin) and thus a functional Fe deficiency. Serum [Fe] is normal |
|
|
Term
| What type of anemia is most common in animals with cobalamin deficiency? |
|
Definition
normocytic, normochromic, nonregenerative anemia
**animals may have megaloblastic cells in BM, but do not typically have a macrocytic anemia (although there may be some peripheral macrocytic RBC, esp in dogs) |
|
|
Term
| What type of anemia is most common in animals with cobalamin deficiency? |
|
Definition
normocytic, normochromic, nonregenerative anemia
**animals may have megaloblastic cells in BM, but do not typically have a macrocytic anemia (although there may be some peripheral macrocytic RBC, esp in dogs) |
|
|
Term
| What changes to the myeloid lineages have been observed in dogs (giant schnauzer) with inherited cobalamin deficiency? |
|
Definition
| hypersegmented neutrophils and giant neutrophils |
|
|
Term
| Deficiency in what B vitamin other than cobalamin has resulted in anemia in kittens? |
|
Definition
|
|
Term
| Describe the pathogenesis of NNN anemia in dogs with hypothyroidism? |
|
Definition
| Decreased T3 and TT4 --> decreased metabolic rate --> decreased O2 demand by tissues --> decreased EPO production ---> anemia |
|
|
Term
| What neoplasms are associated with excess production of estrogen, and hence, severe non-regenerative anemia +/- pancytopenia? |
|
Definition
| sertoli cell tumors (male) and granolas cell tumors (female) |
|
|
Term
| What are the morphologic features of the anemia associated with dyserythropoiesis in English Springer Spaniels? What are the bone marrow findings? |
|
Definition
microcytic, normochormic, nonregenerative anemia with rubricytosis, spherocytes, codocytes, dacryocytes, schistocytes and vacuolated erythrocytes
Bone marrow- ineffective erythropoiesis: hyperplasia of proliferative erythroid cells, frequent binucleate cells and mitotic figures, macs that have phagocytized RBC precursors and abundant Fe |
|
|
Term
| What are the laboratory and bone marrow features of congenital dyserythropoiesis and progressive alopecia of polled herefords? |
|
Definition
macrocytic, normochromic, non-regenerative anemia with rubricytosis (increased serum [Fe], normal TIBC (transferin)
BM: erythroid hyperplasia with dysplasia (multinucleation, megaloblastic cells, irregular chromatin, nuclear budding) with maturation arrest in late rubricate stage. Abundant hemosiderin. |
|
|
Term
| What is expected serum [Fe] and [Ferritin] in animals with Fe deficiency? |
|
Definition
both decreased*
*although ferritin is a positive acute phase protein, so if there is concurrent inflammation it may not be decreased |
|
|
Term
| What infectious agents are most commonly associated with hemolysis? |
|
Definition
Mycoplasma sp., babesia*, theileria*, Ehrlichia, clostridial infections (horses), equine infectious anemia, Anaplasma marginale/centrale (cattle)
*other mechanisms may also contribute to the anemia in these diseases |
|
|
Term
| What is the major proposed mechanism for acute tubular degeneration that has been observed with intravascular hemolysis (hemoglobin nephropathy)? |
|
Definition
Primarily due to altered renal blood flow and exposure of erythrocyte stroma (which may release vasoactive substances or induce DIC/consumptive coagulopathy)
*Free Hgb can also be toxic to proximal tubular epithelial cells (at least experimentally in rats), but this is thought to play a lesser role than altered vascular elements. |
|
|
Term
| What are the pathways for Fe conservation following intravascular hemolysis? |
|
Definition
1. Free Hgb dissociates into dimers and binds to haptoglobin, these complexes are removed by hepatocytes (and maybe also macrophages) and degraded into Fe, Bu, and amino acids.
2. If the haptoglobin concentration is decreased free hemoglobin oxidizes to methemoglobin and dissociates into metheme and globin. The metheme binds to hemopexin and these complexes are removed and degrade by hepatocytes. |
|
|
Term
| What inherited disorder resulting in decreased RBC ATP production is associated with hemolytic anemia in dogs and cats? |
|
Definition
| Pyruvate kinase deficiency |
|
|
Term
| What antibody isotype is usually associated with cold agglutination vs. warm (i.e. body temp) agglutination? |
|
Definition
Cold is usually IgM
Warm is usually IgG |
|
|
Term
| What are the three major mechanisms through what drugs can induce immune hemolysis? |
|
Definition
1. drug adsorption, drug binds covalently to RBC membranes and simulates hapten-dependent Ab.
2. Drug induces formation of autoAb for RBC membrane proteins which bind to RBC in the absence of the drug.
3. drug induces formation of Ab that bind to erythrocytes only when the drug is present. |
|
|
Term
| Mares and queens of which blood types, are associated with neonatal isoerythrolysis in their offspring? |
|
Definition
Mares that are Aa or Qa negative with foals that are Aa or Qa positive
Queens that are B positive with kittens that are A or AB
*alloantibodies are transmitted to offspring through colostrum |
|
|
Term
| Why are mules with a donkey sire more likely to develop neonatal isoerythrolysis than those with a donkey dam? |
|
Definition
| All horses lack immunogenic donkey factor |
|
|
Term
| What are the mycoplasma species that infect pigs, cattle? |
|
Definition
pigs: M. haemosuis and M. parvum
Cattle: M. wenyonii |
|
|
Term
| In which species is hemolysis associated with leptospirosis infections? |
|
Definition
food animals (cattle, small ruminants, pigs)
*pathogenesis is not know but NOT associated with direct infection of RBC. Maybe secondary to liptospiral phospholipase activity or and immunologic response |
|
|
Term
| What species of clostridium are associated with hemolysis in ruminants? What are the pathogenicities of the hemolysis? |
|
Definition
C. haemolyticum and C. novyii type D [RBC damage is cause primarily by a beta-toxin that has phospholipase C or lecithinase activity which degrades RBC membranes causing hemolysis]
C. perfringens type A (aka C. welchii) [Alpha-toxin has phospholipase C activity (damages RBC membranes as well as WBC, PLT, endothelial cells and myocytes)]
**C. perfringens type A has also been associated with hemolysis in horses |
|
|
Term
| What is the most common species of theileria that infects cattle in the USA? |
|
Definition
Theileria buffeli
**highly pleomorphic intracellular piroplasms |
|
|
Term
| What is the name for trypanosoma life stages that can be observed in blood smears? in tissues? |
|
Definition
in blood: free living flagellated trypanomastigotes
in tissues: amastigotes in pseudocysts or macrophages (looks like leishmania, can use PCR to distinguish). |
|
|
Term
| Which species of trypanosoma is most common in cattle in the USA? What its pathogenicity? |
|
Definition
| T. theiler, considered non-pathogenic |
|
|
Term
| Which species of trypanosoma infects dogs and cats in south/central america and southern USA? |
|
Definition
T. cruzi
*trypanomastigotes can be observed in peripheral blood in acute stages, but usually amastigotes are found in nonhemic tissue (brain, heart, lymph node) and hemolytic anemia is not a features of the disease. |
|
|
Term
| Which species of trypanosomes have been associated with hemolytic anemia? |
|
Definition
T. vivax (cattle), T. congolense (cattle, sheep)
**These are both african trypanosomes |
|
|
Term
| What is the major reductive pathway in RBC and what is the rate limiting enzyme in this pathway? |
|
Definition
hexose monophosphate shunt (generates NADPH to maintian GSH in a reduced state, which maintains Hgb and other proteins in a reduced (functional) state)
rate limiting enzyme is G6PH |
|
|
Term
| Describe the pathogenesis of heinz body formation. |
|
Definition
| oxidative injury results in oxidation of Fe in Hgb to Fe+3 --> Hgb-Fe+3 undergoes spontanoues conformational change to form hemichromes (nitrogenase bases of globin chains are bound to Fe+3) or heme depleted Hgb. Hemichromes + heme depleted Hgb precipitate and oxidize sulfhydryl groups to form disulfide bonds. |
|
|
Term
| how can heinz bodies induce a component of immune mediated hemolysis? |
|
Definition
| binding of hemichromes (abnormally conformed oxidized (Fe+3) hemoglobin) to band 3 proteins of the RBC membrane cause a redistribution of these proteins and formation of an antigen that is recognized by autologous antibodies --> extravascular hemolysis |
|
|
Term
| What are some theories as to why cats may be more likely to form heinz bodies than other species? |
|
Definition
feline Hgb has more sulfhydryl groups than other species so it may be prone to forming more disulfide bridges and thus more denatured Hgb.
Cats have less reductive capacity
The anatomy of cat spleens (closed circulation) is less efficient at removal of heinz bodies from circulation. |
|
|
Term
| What dietary component of moist food can cause heinz body formation (but not clinically significant anemia)? |
|
Definition
|
|
Term
| What spontaneous diseases have been associated with increased heinz bodies in cats? |
|
Definition
| hyperthyroidism, diabetes mellitus, lymphoma |
|
|
Term
| What inherited disorders in the RBC hexose monophosphate shunt can result in eccentrocyte formation and hemolysis in horses? |
|
Definition
| G6PD and FAD deficiencies |
|
|
Term
| What breeds of dogs and cats are associated with pyruvate kinase deficiency? What is the end result of this deficiency? |
|
Definition
dogs: basenji, beagle, cairn terrier, west highland white terrier, american eskimo, dachshund)
cats: abyssinian and somali
impaired RBC ATP generation --> hemolysis. Pancytopenia can occur in later stages if myelofibrosis develops |
|
|
Term
| Deficiencies in which enzymes are associated with hemolytic anemia in dogs due to impaired RBC generation of ATP? |
|
Definition
pyruvate kinase deficiency (many breeds)
phosphofructokinase deficiency (spaniels)- acute hemolysis only with hyperventilation and respiratory alkalosis, most of the time hemolysis is mild and compensated. Also impaired downstream formation of 2,3-DPG which is involved in modulated hemoglobin O2 affinity |
|
|
Term
| What is the rate limiting enzyme of the anaerobic glycolysis performed by RBC? |
|
Definition
|
|
Term
| Why do dogs with PFK deficiency often not have anemia (or only a mild regenerative anemia)? |
|
Definition
| PFK deficiency is also associated with 2,3- DPG deficiency. Decreased 2,3-DPG results in increased O2 affinity for Hgb and thus decreased O2 delivery to tissues --> increased EPO production and a compensated hemolytic state |
|
|
Term
| What physiologic state precipitates an acute hemolytic crisis in dogs with PFK deficiency? |
|
Definition
hyperventillation (e.g exercise, excitement)
hyperventillation --> decreased paCO2 --> increased blood pH --> PFK deficient RBC are more susceptible to alkaline fragility than normal RBC (but they are also subject to lysis in alkaline environmens e.g advia/sysmex base chanel) |
|
|
Term
| How does hypophosphatemia (e.g. post-parturient in cattle, insulin therapy in DKA dogs) cause hemolysis? |
|
Definition
| hypophosphatemia --> impaired RBC ATP production |
|
|
Term
| What is the pathogenesis of hemolysis in dogs with L-sorbose intoxication? |
|
Definition
dog breeds with low intraerythrocyte [K+] become ATP depleted. This occurs due to inhibition of hexokinase (catalyzes glucose --> G-6-P) by sorbose-1-phosphate
**sorbose-1-phosphate is also formed in RBC with high [K+] but has less of an inhibitory effect on hexokinase |
|
|
Term
| What enzyme is involved in incorporation of Fe+2 into heme during hemoglobin synthesis? |
|
Definition
|
|
Term
| What B vitamin is involved in hemoglobin synthesis? |
|
Definition
B6 (pyridoxine) is a cofactor in the initial reaction of glycine and succinyl CoA to delta ALA*
**the beginning of the porphyrin ring formation |
|
|
Term
| What is the most common type of poryphria in animals? |
|
Definition
Acquired hepatic porphyria. Hepatic disease results in impaired degradation and excretion of dietary (usually plant/chlorphyl derived) porphyrins --> photosensitization and anemia *not all porphyrias are associated with anemia*
**lead poisoning is also an acquired porphyria, typically not associated with anemia however |
|
|
Term
| Which of the hereditary poryphrias have been associated with anemia? |
|
Definition
bovine congenital erythropoietic porphyria (holsteins, short horn, jamaican)- autosomal recessive, deficiency in uroporphyrinogen III cosynthase
feline erythropoietic porphyria (siamese)- mode of inheritance and specific enzymatic defect not identified. Photosensitivity, hemolytic anemia and renal disease.
**other congenital erythropoietic porphyrias have been described in cattle, pigs, and cats, but are not associated with anemia |
|
|
Term
| Describe the mechanism of anemia associated with porphyria (acquired or congenital)? |
|
Definition
**not all forms of porphyria cause hemolytic anemia**
For those that are associated with anemia, porphyrins may damage RBC membrane lipids and may also experience oxidative damage and lysis if exposed to UV light in surface capillary beds |
|
|
Term
| In what species can heparin (administered as anticoagulant therapy) induce hemolysis? |
|
Definition
| horses *typically the anemia is only mild to moderate, pathogenesis is unknown |
|
|
Term
| What toxin in the venom of some poisoning snakes and insects is associated with hemolysis? |
|
Definition
phospholipase a2
**snake envenomation, depending on the species, can also be associated with complement mediated hemolysis (e.g. cobra venom factor) |
|
|
Term
| In what dog breed has a hereditary, non-spherocytic, hemolytic anemia been reported? |
|
Definition
Beagles- specific defect has not been identified
**affected individuals have increased RBC osmotic fragility and shortened RBC lifespans --> BM erythroid hyperplasia, mild anemia with persistent reticulocytosis, splenomegally |
|
|
Term
| In what cats breeds has a hereditary, non-spherocytic, hemolytic anemia been reported? |
|
Definition
Abyssinian and somali (also prone to PK deficiency)
due to increased osmotic fragility, persistent regenerative anemias and splenomgeally. Specific defect has not yet been identified. |
|
|
Term
| What toxin may be associated with hemolysis and liver disease in horses? |
|
Definition
| pyrrolizidine alkaloid toxicity |
|
|
Term
| What endocrinopathy is associated with secondary appropriate rubricytosis? |
|
Definition
feline hyperthyroidism
*increased metabolic rate --> increased need for O2 delivery to tissues, HCT of 38-57% reported in 45% of hyperthyroid cats (n=131) in one study |
|
|
Term
| What breeds of horses and dogs have higher HCT compared to other breeds of their species? |
|
Definition
warm blooded horses (TB, Standardbred, QH) have higher HCT than draft horses
Sighthounds have higher HCT than most other dog breeds |
|
|
Term
| Deficiency in which enzymes have been associated with congenital methemoglobinemia? |
|
Definition
cytochrome b5 reductase deficiency (dogs and cats)
FAD and glutathione reductase deficiencies (horses)
**can reduce Fe in Hgb --> methemoglobinemia (Fe+3) |
|
|
Term
| What is a frequent cause of acquired methemoglobinemia in ruminants? |
|
Definition
nitrate poisoning
**ingestion of feed with high nitrate content --> increased rumenal formation of nitrite (NO2-) which binds to oxyhemoglobin releasing O2 and inciting reactions that form methemoglobin (Hgb-Fe+3) amongst others (hydrogen peroxide, NO2 radical and more NO2-) |
|
|
Term
| How can blood gas analysis be used to detect the presence of methemoglobinemia? |
|
Definition
SO2 will be decreased but SPO2 (pulse oximetry) will be normal because the pulse oximeter cannot differentiate Hgb-Fe+3 from oxyhemoglobin
**could also use a Co-oximeter which can differentiate oxyhemoglobin, deoxyhemoglobin, carboxyhemoglobin and methemoglobin by their different absorption spectra of light. |
|
|
Term
| What are the classic features of cytochrome b5 reductase deficiency in dogs? |
|
Definition
clinical signs of hypoxia
methemoglobinemia (dark to chocolate blood) often with heinz bodies
No anemia or mild anemia +/- compensatory reticulocytosis |
|
|
Term
| What is the proposed mechanism of stomatocyte formation in schnauzers with hereditary stomatocytosis? |
|
Definition
Erythrocyte over hydration due to defective cation exchange (RBC [Na] and [K] were increased), typically not anemic
**probably different mechanism of stomatocytosis in the other 2 affected dog breeds (chondrodystrophic malamutes and drentse patrijshonds) |
|
|
Term
| What are the normal functions of erythrocyte membrane protein Erythrocyte band 3? |
|
Definition
- ion exchange protein (exchange of HCO3- (out) and Cl- (in) to transport CO2 from tissues to lungs (carbonic anhydrase reaction))
-contributes to RBC cytoskeleton
**band 3 deficiency in Japanese black cattle results in chronic hemolytic anemia with spherocytes and metabolic acidosis |
|
|
Term
| What is the pathogenesis of hereditary eliptocytosis in dogs? |
|
Definition
defective and deficient erythrocyte membrane protein 4.1 (normally stabilizes the cytoskeleton by providing an anchor for specter-ankyrin complexes)
usually slight anemia with moderate reticulocytosis, in general no significant clinical effect |
|
|
Term
| What is the normal function of erythrocyte membrane protein 4.1? |
|
Definition
| stabilizes the RBC cytoskeleton by serving as an anchor for the spectrin-ankyrin complexes |
|
|
Term
| What is the normal function of spectrin? |
|
Definition
spectrin is a major RBC cytoskeletal protein, it consists of two heterodimers (alpha and beta) which self associate to form tetramers.
*molecular defects typically reduce the association of dimers into tetramers in the RBC membrane --> poikilocytosis (spherocytes or elliptocytes). In dogs spectrin deficiency or abnormalities are not associated with clinically significant anemia |
|
|
Term
| What dog breed is associated with hereditary spectrum deficiency? |
|
Definition
dutch golden retrievers
*not associated with spherocytosis or clinically significant anemia |
|
|
Term
| In cats what is the most common disease process associated with megaloblastic anemia? |
|
Definition
|
|
Term
| What bone marrow findings are consistent with sideroblastic anemia? |
|
Definition
>15% sideroblasts in the bone marrow and ringed sideroblasts
*there is also typically bone marrow dysplasia which can affect all lineages. Normal to increased bone marrow Fe. |
|
|
Term
| What underlying diseases are associated with sideroblastic anemia in dogs? |
|
Definition
| indicate defective Fe metabolism, and have been reported in association with acute hepatitis, pancreatitis, glomerulonephritis, sepsis and myelofibrosis. |
|
|
Term
| When in the course of disease are canine distemper virus inclusions appreciable in peripheral blood (RBC, neuts, lymphs)? |
|
Definition
| early viremic stage, typically before clinical signs are evident |
|
|
Term
| With regards to feline blood typing cards how are type A and type B antigens detected? |
|
Definition
Type A is detected with an agglutinating antibody
Type B is detected with wheat germ lectin |
|
|
Term
| Which of the cross matching procedures assesses for the presence of antibodies in the recipient's plasma? in the donor's plasma? |
|
Definition
Ab in recipient plasma: Major cross match (donor RBC, patient serum)
Ab in donor plasma: Minor cross match (donor serum, patient RBC) |
|
|
Term
| Which dog erythrocyte antigen is associated with naturally occurring antibodies when positive blood is given to negative recipients? |
|
Definition
DEA 3
20% of DEA 3 negative dogs may have naturally occurring antibodies, Only 6% of US dogs are DEA 3 |
|
|
Term
| Which erythrocyte antigens in horses are most often associated with nature isoantibodies in negative individuals? |
|
Definition
| equine erythrocyte antigen Aa and Ac |
|
|
Term
| What concurrent hematologic abnormalities is often associated with protozoal infections of erythrocytes? |
|
Definition
thrombocytopenia
*likely associated with increased phagocytosis of platelets due to antibodies present on platelet surface and/or macrophage activation by inflammatory cytokines (e.g. M-CSF, IFN-gamma) |
|
|
Term
| Infections with which erythrocyte parasites are NOT typically associated with thrombocytopenia? |
|
Definition
| anaplasma and hemotropic mycoplasmas |
|
|
Term
| Which of the babesia species can cause severe hemolytic anemia in immunocompetent dogs? |
|
Definition
B. gibsoni, B. conradae (both have small piroplasms)
*B. canis has three genetically distinct subspecies, of which B. canis rossi causes severe disease in adult dogs (limited to South Africa).
B. canis vogeli is the large babesia piroplasm observed in the USA and can cause severe hemolytic anemia in pups, but typically mild or innaparent disease in immunocompetent adults |
|
|
Term
| What are the two most important babesia sp. infecting cattle? What is their pathogenicity? |
|
Definition
B. bigemina (look like B. canis) and B. bovis
both can cause life threatening hemolytic anemia |
|
|
Term
| What are the two most important babesia sp. infecting horses? What is their pathogenicity? |
|
Definition
B. caballi (large piroplasm, look like B. canis) and B. equi (smaller, more pleomorphic piroplasm, eg. maltese cross, signet ring etc.)
*B. equi is more pathogenic than B. caballi |
|
|
Term
| What is the pathogenicity of theileria sp. in ruminants in the USA? |
|
Definition
generally low (theileria can infect cattle and cervids)
**occaisionally hemolytic anemia in infected deer, cattle in africa/asia/middle east often have anemia with infections(t. para, T. annulata)
*T. bufeli has been reported to cause hemolytic anemia in cattle in the USA, piroplasms are extremely pleomorphic (almost look like mycoplasma) |
|
|
Term
| Which of the anaplasma species in cattle is most pathogenic? How does age of infected cow alter the clinical manifestation of disease? |
|
Definition
A. centralis is less pathogenic than A. marginale
infected calves typically develop asymptomatic disease (and can serve as reservoirs), while infected adults can develop mild to severe (fatal) hemolytic anemia |
|
|
Term
| What concurrent conditions are associated with the presence hemolytic anemia and hemotropic mycoplasma organisms in blood smears from dogs? |
|
Definition
| Splenic pathology/previous splenectomy, immunosuppression |
|
|
Term
| What mycoplasma species can produce hemolytic anemia in splenectomized cattle? |
|
Definition
|
|
Term
| What oxidant containing plants can cause hemolytic anemia when ingested by cattle? By horses? |
|
Definition
Cattle: kale, brassica sp., lush winter rye
horses (and palaces): wilted red maple leaves |
|
|
Term
| In what species is copper toxicity associated with heinz body formation (and hemolytic anemia)? |
|
Definition
|
|
Term
| What is the most important component of venoms (snakes, insects, spiders) that contributes to the formation of hemolytic anemia? |
|
Definition
| phospholipase enzymes (esp. phospholipase A2) |
|
|
Term
| How does RBC 2,3-DPG concentration (e.g. in association with PFK deficiency) affect the potential for intravascular hemolysis? |
|
Definition
RBC with low 2,3-DPG concentrations are more alkaline fragile and prone to lysis at physiologic pH.
*decreased 2,3-DPG (due to decreased PFK activity) is associated with increased O2 affinity for Hgb |
|
|
Term
| What dog breeds have the highest incidence of pyruvate kinase deficiency? What is the clinical manifestation and disease progression? |
|
Definition
Basenji and beagles-
Young animals have markedly regenerative hemolytic anemia --> as dogs age myelofibrosis and osteosclerosis develops in BM, hemochromatosis and cirrhosis develop in the liver. Affected individuals typically die between 1-5yrs due to pancytopenia or liver failure |
|
|
Term
| What cat breeds have the highest incidence of pyruvate kinase deficiency? What is the clinical manifestation and disease progression? |
|
Definition
Abyssinian, Somali, also reported in DSH
*cats are often asymptomatic but intermittent severe hemolytic crisis can develop. Bone marrow and liver failure have not been reported (in contrast to dogs), so life expectancy in affected cats is generally longer compared to dogs |
|
|
Term
| How can pyruvate kinase deficiency be diagnosed in dogs? In cats? |
|
Definition
Can measure PK activity in RBC or look for a specific mutation.
Difficult to dx in dogs because their RBC have an unstable PK isoenzyme (M2) that is usually lost as erythroid precursors develop into mature RBC, and several different genetic mutations have been identified. There are PCR assays specific to certain dog breeds.
Cats all have the same mutation and a single DNA based PRC test is available for dx. |
|
|
Term
| PFK deficiency has been reported in which dog breeds? What is the clinical manifestation? |
|
Definition
Spaniels! (english springer and american cocker, german wachtelhund) also mixed breed dogs and whippets
homozygous individuals have persistent compensated hemolytic anemia (HCT ~30-40%) with sporadic episodes of intravascular hemolysis. <-- can be precipitated by hyperventilation induced alkalemia because PFK deficiency -> 2,3-DPG deficiency and increased alkaline fragility of RBC |
|
|
Term
| How can PFK deficiency be diagnosed in dogs? |
|
Definition
measure RBC PFK activity (dogs >3months old)
PCR test has been developed to distinguish affected, carrier, and clear, but Wachtelhunds have a different mutation so cannot be typed with this test. |
|
|
Term
| How does the clinical manifestation of increased RBC fragility differ from PK deficiency in Abyssinian and Somali cats? |
|
Definition
increased RBC fragility (suspect membrane defect) is associated with persistent moderate to severe anemia and rarely intravascular hemolysis
PK deficiency is associated with normal to mildly decreased HCT and intermittent episodes of severe hemolytic crisis.
**can differentiate definitively with PCR test for PK deficiency |
|
|
Term
| Deficiency in what protein is associated with hereditary spherocytosis in Japanese Black cattle? |
|
Definition
Band 3 (RBC membrane protein) deficiency --> severe hemolytic anemia shortly after birth, mild hemolytic anemia with persistent marked spherocytosis in surviving individuals
*homozygous and heterozygous affected have increased RBC osmotic fragility |
|
|
Term
| What inherited diseases in horses are associated with altered function of the hexose monophosphate shunt pathway for RBC glycolysis? |
|
Definition
glucose-6-phosphate dehydrogenase deficiency
FAD deficiency
*G6P deficiency associated with persistent hemolytic anemia vs. FAD deficiency associated with normal to mildly decreased HCT but persistent methemoglobinemia. |
|
|
Term
| What condition is associated with macrocytosis and hypochormasia in non-anemia dogs without reticulocytosis? |
|
Definition
hereditary stomatocytosis (malamutes (also chondrodystrophic), schanuzers and pomeranians (both associated with RBC overhydration due to altered cation exchange, increased intra-RBC [Na] and [K])
*in affected drentse patrijshonds there is typically anemia and reticulocytosis compared to the other breeds. RBC from all affected breeds have increased osmotic fragility and shorted RBC lifespan |
|
|
Term
| Failure of what organ system in horses is associated with marked intravascular hemolysis? |
|
Definition
liver failure
*mechanism is unknown, possibly bile salts and bile acids could be hemolytic factors in horses |
|
|
Term
| What are some mechanisms that contribute to the risk of postparturitent hemoglobinuria in dairy cattle? |
|
Definition
hypophosphatemia --> decreased RBC ATP production
concurrent copper deficiency --> increased susceptibility of RBC to oxidative injury |
|
|
Term
| What four conditions have been associated with microcytic, non regenerative anemia? |
|
Definition
Defective heme synthesis: Fe deficiency, Copper deficiency, pyridoxine (Vit B6) deficiency
Abnormal erythoid maturation: congenital dyserythropoeisis in English springer spaniel |
|
|
Term
| What five conditions have been associated with macrocytic, non regenerative anemia? |
|
Definition
FeLV
myelodysplasia
erythroleukemia
folate deficiency
dyserythropoiesis in polled herford calves |
|
|
Term
| What hematologic findings are associated with cobalamin deficiency in dogs? |
|
Definition
normocytic nonregenerative anemia
neutropenia with hypersegmented neutrophils
giant platelets |
|
|
Term
| What conditions are associated with nonregenerative anemia due to disorders in nucleic acid synthesis? |
|
Definition
folate deficiency --> macrocytic nonregenerative anemia in pigs and a cat
Cobalamin deficiency (secondary to inherited defects in cobalamin absorption in dogs and cats) --> NORMOCYTIC nonregenerative anemia (also neutropenia with neutrophil hyper segmentation and giant platelets) |
|
|
Term
| What conditions are associated with nonregnerative anemia due to abnormalities in heme synthesis? |
|
Definition
Fe deficiency (usually secondary to chronic blood loss)
Copper deficiency (copper is a component of the enzymes haphaestin (enterocytes) and ceruloplasmin (plasma, Fe from macrophages) that oxidize Fe+2 --> Fe+3 for binding to transferin)
Pyridoxine (vit B6) deficiency (only experimentally in dogs, cat, pigs)- pyridoxine is a cofactor in the rate limiting enzyme in heme synthesis (5-aminolevulenic acid synthase) |
|
|
Term
| What conditions are associated with selective erythroid aplasia/pure red cell aplasia? |
|
Definition
congenital (rare)
acquired:
-immune mediated destruction of erythroid stem cells
-FeLV subgroup C (binds to heme exporter on bone marrow colony forming unit erythroid, free heme accumulates and is toxic)
-drugs (chrloramphenicol, may be reversible in dogs, non-reversible in cats; recombinant erythropoietin, Ab cross react with endogenous EPO) |
|
|
Term
| What is the definition of primary erythrocytosis (aka polycythemia vera)? |
|
Definition
erythrocyte proliferation in the presence of normal or low EPO concentrations- dx of exclusion
*primary erythrocytosis is more appropriate in animals because the proliferation is typically limited to erythrocytes (as opposed to humans where all cell lines are often affected). |
|
|
Term
| What is the cut-off value for MCV, below which Fe deficiency is most likely? |
|
Definition
52 fL
**other causes of microcytosis (e.g. portosystemic shunt, inflammation) do not result in MCV this low, however, many cases of Fe deficiency are also not this small. |
|
|
Term
|
Definition
| embyonic precursors for blood vessel and hematopoietic cells, derived from yolk sac |
|
|
Term
| How does fetal hemoglobin differ from that of adult animals? |
|
Definition
Fetal hemoglobiln has lower levels of 2,3-DPG (and therefore higher O2 affinity) compared to adult hemoglobin.
** 2,3-DPG increases to adult levels within a few days after birth to facilitate oxygen delivery to tissues |
|
|
Term
| What molecules are important in erythroid specific gene regulation during embryonic/fetal hematopoietic development? |
|
Definition
| GATA-binding protein 1, 2, 4 |
|
|
Term
| What molecule is important in regulating definitive (adult) hematopoiesis? |
|
Definition
| stem cell leukemia/T-cell acute leukemia factor 1 (Scl/Tal-1) |
|
|
Term
| What roles does purine box-binding transcription factor 1 (PU.1) play in embryonic/fetal hematopoiesis? |
|
Definition
increased PU.1 --> early macrophage development and development of myeloid progenitors
decreased PU.1 --> development of normal erythroid, megakaryocyte, and lymphocyte precursors |
|
|
Term
| What role does Indian Hedgehog play in embryonic/fetal hematopoietic development? |
|
Definition
|
|
Term
| What role does bone morphogenetic protein 4 play in embryonic/fetal hematopoietic development? |
|
Definition
| vasculogenesis in yolk sac |
|
|
Term
| What roles does beta 1 vs. beta 4 integrins play with regards to fetal hematopoiesis? |
|
Definition
beta1 integrins are involved in the adhesive interaction between hematopoietic stem cells and enfothelium
beta4 integrins are involved in homing, differentiation, and expansion of erythroid and B lymphocyte precursors later in fetal development |
|
|
Term
| When MCHC is within the reference interval, what should the numerical values of the measured blood HGB concentration be? |
|
Definition
| measured HGB should be approximately 1/3 of the numerical HCT value if MCHC is WRI |
|
|
