Term
Define intramedullary hematopoiesis in skeletal bone
-the 5 processes in hematopoiesis |
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Definition
Bone marrow is the site of hematopoiesis after birth
All mature red cells derive from pleuripotential stem cells in BM
Erythropoiesis
Granulocytopoiesis
Monocytopoiesis
Lymphoctyopoiesis
Thrombocytopoiesis |
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Term
| Define the sites for extramedullary hematopoiesis, esp. the spleen |
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Definition
Hematopoiesis occurring outside the medulla (bone in marrow trabecular bone) of the bone
may be physiologic, e.g. during fetal development (liver, spleen)
frequently associated with pathologic processes |
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Term
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Definition
(pronormoblast)
largest
deep blue cytoblasm - lots of rRNA, affinity for basic dyes
free cytoplasmic ribo synthesize Hb
nuclear chromatin is euchromatic |
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Term
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Definition
intensely basophilic cytoplasm
more heterochromatic nucleus
ribo synthesize Hb |
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Term
| orthochromatophilic erythroblast |
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Definition
higher Hb content
-cytoplasm more eosinophilic
small, densely stained pyknotic nucleus is seen as it is extruded from the cell
in this stage, the RBC precursor loses the nucleus |
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Term
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Definition
the erythroid cell in the peripheral blood in a phase of maturation
nucleus has been removed, but some extranuclear RNA remains (slight basophilia)
Residual RNA is generally lost during the 24 hrs after the cell enters the circulation
The spleen removes the residual RNA as the immature cells circulate
Have a more convoluted shape, are ~8% larger than the more mature cells
aka "polychromasia"
these cells circulate
A polychromatic red cell (reticulocyte)
-somewhat larger than RBC
-bluish color (RNA content)
-sig higher % means i/c BM production |
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Term
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Definition
smallest
RBC remain in BM 2-3 days until fully mature
loss of nucleus, all organelles
biconcave |
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Term
| Erythropoiesis - describe the changes in RBC size, RNA content, Hb content with maturation |
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Definition
red cell precursors get smaller
iron (Hb) content increases (more eisinophilic)
protein synthesis/RNA content decreases (less basophilic) |
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Term
| Discuss the length of time red cells circulate in the blood and the percent of the total red cell pool released into the blood each day (the reticulocyte count) |
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Definition
RBC circulate in the blood ~120 days
0.5-2.5%
(the # of reticulocytes reflects bone marrow production) |
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Term
Discuss the maturation of reticulocytes to mature erythrocytes in the peripheral blood
note the spleen will remove any abnormal cytoplasmic particles |
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Definition
orthochromatophilic normoblast -->
nucleus extruded from cell -->
reticular fibers are removed from reticulocyte -->
RBC
polychromasia: a circulating reticulocyte; polychromatophilic RBC
the duration of a reticulocyte in the circulating blood is 1 day |
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Term
| list the morphologic characteristics of a reticulocyte on both Wright stain and special supravital stain |
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Definition
On a supravital stain - polyribosomes/RER clump to form a blue granular network called reticulum when stained with a supravital dye; these circulating immature RBCs are reticulocytes (spleen will remove the residual RNA network)
Wright stain - used for routine exam; only the earliest reticulocytes with the most residual RNA will be "polychromatophil" (more bluish than the mature erythrocytes); appear as macrocytes with diffuse cytoplasmic basophilia (polychromasia) with this stain |
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Term
| describe the shape, size, and coloration of mature circulating erythrocytes |
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Definition
uniform in size (~ same size as nucleus of a small lymphocyte)
biconcave discs |
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Term
| Recognize & explain nucleated RBC in a peripheral blood smear |
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Definition
Nucleated red cells don't normally appear in peripheral blood
if they are seen - consider a marked i/c in marrow erythroid production (acute hemorrhage, hemolysis); or a marrow infiltrative process (tumor cells, fibrosis)
newborns have nucleated RBC |
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Term
| The disorder that you see with so much hemolysis that you see nucleated RBC? |
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Definition
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Term
| Understand the normal development & differentiation of erythroid cells and the role growth factors have on the development of hematopoietic cells |
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Definition
Proerythroblast ->
Basophilic erythroblast ->
Polychromatic erythroblast ->
Orthochromatic erythroblast ->
(nuclear extrusion)
Reticulocyte ->
Erythrocyte |
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Term
| Define erythropoietin; discuss the role of erythropoietin in erythropoiesis |
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Definition
Kidneys release erythropoietin, usually in response to hypoxia.
Erythropoietin acts in BM to stimulate erythropoiesis
atmospheric O2, Hb conc, blood volume, cardiopulmonary function, O2 affinity all affect juxtaglomerular O2 sensors, which affect erythropoietin producers |
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Term
| Discuss the relationship of the bone marrow response to anemia and the release of reticulocytes |
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Definition
Look for reticulocytes, bone marrow hyperplasia in anemia
Anemia stimulates the release of erythropoietin from kidneys, increases the # of reticulocytes
In renal failure - don't have enough erythropoietin, so not enough RBC |
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Term
| what would be a bone marrow finding in a patient with hemolytic anemia, who has a lot of reticulocytes? |
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Definition
Bone marrow hyperplasia
- erythropoietin stimulates bone marrow
- erythroid cells increase
- evidenced by increased reticulocyte count |
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Term
What is aplastic anemia?
What would you expect to find in CBC? |
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Definition
Failure or suppression of bone marrow or stem cells in the bone marrow; leads to anemia, thrombocytopenia, and neutropenia - bone marrow failure
Expect high erythropoietin, low reticulocyte count, pancytopenia |
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Term
| Describe & recognize the functional anatomy & histology of the spleen as a part of lymphoid system and the mononuclear phagocytic system |
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Definition
macrophages are identified in the red pulp of spleen by ingested RBC debris
HISTO: in red pulp the sinusoids are separated by the splenic cords (of Bilroth)
as blood percolates through the splenic cords macrophages remove old platelets and RBC (macrophage "cherry pickers") |
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Term
Recognize the histo & function of the splenic pulp
- red pulp
- Bilroth's cords |
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Definition
RED PULP OF SPLEEN:
composed of splenic sinuses and splenic cords
place where macrophages are getting rid of old RBC
the Sinuses are the spaces b/t the Cords where the blood filters through
The venous sinuses (sinusoids) have large lumens, with the lining cells protruding into lumen
CORDS OF BILROTH:
Lie b/t the splenic sinusoids
contain erythrocytes
blood from the venous sinuses is drained by pulp veins, lead into trabecular veins
RBC have to squeeze from red pulp into sinus lumen - requires deformability for red cells to pass through wall of sinus |
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Term
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Definition
RBCs lyse in the circulation, releasing Hb into plasma
-Hb immediately bound by haptoglobin
-Hb-haptoglobin cleared from plasma by hepatic reticuloendothelial cells in the spleen and liver
-generally overwhelms haptoglobin synthesis, haptoglobin levels d/c
-after haptoglobin is saturated, excess Hb is filtered in kidney & reabsorbed in PCT where iron is recovered --> ferritin or hemosiderin
Causes mechanical trauma, complement fixation, and other toxic damage to RBC
Fragmented RBCs are called *schistocytes,* associated with:
-diffuse narrowing of microvasculature (disseminated intravascular coagulation)
-prosthetic heart valve with turbulent blood flow and shear forces |
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Term
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Definition
Blood cells:
-hemoglobin --> heme, globin
-heme is deoxygenated (heme oxygenase) to Biliverdin IX-alpha
-reduced (biliverdin reductase) to Bilirubin (water-insoluble)
Bilirubin carried via blood to LIVER:
bilirubin -(2 UDP-glucoronic acid)-> bilirubin diglucuronide (water-soluble)
Carried via bile duct to INTESTINES:
-urobilinogen formed by bacteria (stercobilin excreted in feces)
Reabsorbed into blood, KIDNEY:
-urobilin excreted in urine |
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Term
Erythrocytes & Spleen - Extravascular Hemolysis
Describe the physiologic destruction of old erythrocytes in the spleen and bone marrow |
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Definition
The physiologic destruction of old erythrocytes in the spleen and bone marrow
-the red pulp of the spleen contains many RBC and macrophages
-allows for phagocytosis of RBC
when red cells are destroyed in the spleen or bone marrow, it's called extravascular hemolysis
intravascular hemolysis - self-destruction, destroyed in the space |
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Term
Erythrocytes & Spleen
- lifespan of RBC |
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Definition
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Term
Erythrocytes & Spleen
-role of the splenic sinusoids and adjacent macrophages in the destruction of red cells |
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Definition
Macrophages in splenic cords phagocytize RBC with:
- old, less deformable red cells
- membrane abnormalities (e.g. bound immunoglobin)
- physical abnormalities restricting RBC deformability that prevent egress from spleen |
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Term
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Definition
Have a small diameter, are darker staining than normal
No pale center like a normal RBC
Spherical shape due to loss of membrane area
more susceptible to osmotic stress and phagocytosis by macrophages in the spleen |
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Term
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Definition
Residual *DNA*
spherical blue bodies (Wright stain) in RBC
portion of nuclear content still in the RBC
should be removed by spleen
if a lot are present, the spleen's not functioning properly or the BM is releasing a lot of abnormal cells |
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Term
| polychromatophilic erythroblast |
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Definition
slate gray cytoplasm
-steady buildup of Hb
-decrease in ribosomes
nucleus has condensed chromatin, no nucleoli |
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Term
| What does petechiae indicate? |
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Definition
Platelet disorder
Look in the BM if you have pancytopenia |
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Term
Determine the intramedullary erythrocyte maturation time (amt of time it takes to mature from a proerythroblast to erythrocyte)
-expected time interval for an optimal bone marrow response to anemia |
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Definition
*7-10 days*
5 days from stem cell to erythroblast to polychromatic erythroblast
Expected time for new cells to enter blood: 5-10 days
Max response is at least 7 days after anemia/blood loss tx |
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Term
| Describe the catabolism of heme (10 steps) |
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Definition
1. senescent RBC are major source of hemeproteins
2. breakdown of heme -> bilirubin occurs in macrophages of the reticulo-endothelial system (tissue macrophages, spleen, liver)
3. Unconjugated bilirubin is transported through the blood (complexed to albumin) to the liver
4. Bilirubin is taken up by the liver and conjugated with glucoronic acid
5. Conjugated bilirubin is secreted into bile, then the intestine
6. In intestine, bacteria removes glucoronic acid. Bilirubin is converted to urobilinogen
7. Some of the urobilinogen is reabsorbed from gut, enters portal blood
8. Portion of urobilinogen participates in the enterohepatic urobilinogen cycle
9. Remaining urobilinogen is transported by the blood to the kidney, where it's converted to yellow urobilin and excreted (makes pee yellow)
10. Urobilinogen is oxidized by intestinal bacteria to brown stercobilin |
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Term
| What does hemoglobinuria indicate? |
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Definition
Severe intravascular hemolysis
-has saturated haptoglobin levels
-has overwhelmed the absorptive capacity of the renal tubular cells |
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Term
| Intravascular hemolysis & JAUNDICE |
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Definition
Haptoglobin is depleted, free Hb is oxidized to methemoglobin (brown in color)
Heme groups not bound to haptoglobin are catabolized to bilirubin --> jaundice
Level of hyperbilirubinemia depends on the functional capacity of the liver and the rate of hemolysis
When liver is normal, jaundice is rarely severe
Excessive bilirubin excreted by liver into GI tract --> i/c formation & fecal excretion of urobilin |
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Term
Describe the products of Hb degradation that appear in the blood and urine
-intravascular hemolysis
-extravascular hemolysis
-which process is more likely to result in iron deficiency anemia? |
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Definition
Intravascular hemolysis --> hemoglobinuria, hemoglobinemia
*NOT seen in extravascular hemolysis*
-more likely to get iron deficiency anemia
-d/c haptoglobin
Extravascular hemolysis --> recycling of AA and iron
-AA from globin chains are recycled
-Fe removed from heme and reused
-heme is degraded into tetrapyrrole, bilirubin
-b/c little Hb escapes into plasma, haptoglobin generally does NOT d/c
-free unconjug bilirubin is transported to liver, conjugated to glucoronic acid
-plasma levels of unconjugated bilirubin i/c only if hepatocytes can't process excess bilirubin |
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Term
| How does hemolytic anemia affect bilirubin levels in the blood? |
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Definition
i/c production of bilirubin
more bilirubin is conjugated & excreted than normal
conjugated mechanism is overwhelmed
abnormally large amt of *unconjugated bilirubin* is found in the blood |
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Term
Compare intravascular & extravascular hemolysis:
-peripheral smear
-haptoglobin
-urine hemosiderin
-urine Hb
-jaundice |
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Definition
Intravascular:
-may have schistocytes
-d/c or absent haptoglobin
-++ urine hemosiderin
-++ urine Hb
-slight jaundice
Extravascular:
-may have spherocytes
-mild d/c haptoglobin
-neg hemosiderin, Hb in urine
-more severe jaundice (breakdown of Hb, i/c in bilirubin) |
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Term
Describe the structures of the red cells that aid in function-transport of O2
-what variables affect the Hb dissociation curve? |
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Definition
Normal Hb molecule is well suited for picking up O2 in the lungs and transporting it to tissues w/o using any
-cooperative binding
-sigmoidal dissociation curve
an increase in CO2, temperature, or 2,3-DPG all d/c O2 affinity, shifting the curve to the right, allowing for increased unloading
-as Hb conc d/c, 2,3-BPG i/c, allowing more O2 to be unloaded |
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Term
CBC
-hematocrit
-mean cell Hb (MCH)
-mean Hb concentration (MCHC)
-what else is included in the CBC?
Also:
-red cell index: how do you measure size?
-total blood Hb |
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Definition
-% of whole blood made up of erythrocytes
-MCH measures amt of Hb per red cell
-MCHC measures amt of Hb per packed cell volume
-WBC count and differential - divides WBC into granulocytes, lymphocytes, monocytes, and abnormal cells
-platelet count
Size measured by mean corpuscular volume (MCV) |
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