Hematopoiesis Flashcards
What are the layers in an aliquot of blood?
- top: plasma
- middle: thin line of WBCs (buffy coat)
- bottom: RBCs (heaviest)
unable to see platelet layer
Normal hematocrit in males and females
- male: 40-50%
- female: 35-40%
Hematocrit trend from newborn to child
Higher HCT in new borns (45-60%) but then drops down to around 35% until the age of 10
Why does hematocrit decrease during pregnancy?
-normally decreased during 3rd trimester d/t volume expansion; have a lot more fluid and plasma
Make up of plasma
- 90% water
- 10% dissolved substances:
- 7% protein
- 2% aa, vitamins, hormones, lipids
- 0.9% inorganic salts
What is the main protein in plasma? (4% of the 7% total)
albumin (plasma also includes immunoglobulins, fibrinogen, prothrombin)
What is “normal saline” that is given for IV fluids based off of?
Normal saline is classified as 0.9% saline d/t our physiologic saline being 0.9% of our plasma
Plasma vs. Serum
- If not centrifuged, blood will clot spontaneously, which uses up the clotting factors leaving the serum with no clotting elements
- Plasma contains all things discussed previously (PA: plasma, all)
Coulter Counter
device to measure blood counts; extremely accurate until you get above 100k WBCs/mL like in leukemia
A blue colored stain in a blood smear indicates why kind of cell?
basophilic
A yellowish-pink stain in a blood smear indicates what kind of cell?
eosinophilic (eosin is red but stains yellow/pink)
A salmon pink stain in a blood smear indicates what kind of cell?
Neutrophilic (Does not take up eosin or basophilic stain)
What is the process that drives erythropoiesis?
Erythrogenin stimulates the transformation of erythropoietinogen to erythropoietin
Erythrogenin
- where produced
- why
- produced by kidney
- in response to hemorrhage, high altitude, anemia, etc.
Erythropoietinogen is produced by what?
liver
Native erythropoietin is produced by what?
kidney
Hemoglobin
-tetramer w/ 2 alpha globin chains and 2 beta globin chains
What produces alpha and beta polypeptides/chains?
mRNA
What is each globin chain bound to in Hgb?
w/ a porphyrin containing iron
Variations in Hgb are d/t what?
differences in aa sequence of globin chains
Most of our circulating hgb is what kind?
alpha 1 (HgbA1)
Steps in the formation of hgb
- 2 CoA + 2 glycine = 4 pyrrole
- 4 pyrrole -> protoporphyrin
- Fe attaches to protoporphyrin to get a heme
- heme insterts into the globin
Fe binding in hgb formation
- 1 heme will insert itself in into every globin chain
- The Fe in heme has 2 binding sites for oxygen
- this means 1 Hgb molecule can carry 8 elemental oxygen atoms (4 O2 molecules)
HgbS
- sickle cell disease
- substitution of aa at position 6 on beta globin chain
Effect of HgbS
- can’t carry O2 as well
- causes conformational change – sickle shaped RBC
HgbF
- primary Hb when born (80%)
- 2 alpha and 2 gamma globin chains
- higher affinity for oxygen
When does the primary Hgb shift from F to A1 ?
- by 6 mos
- 97% now HgbA1
What is significant about HbgF in possible tx for sickle cell?
- gamma globin not effected in sickle cell
- can take hydroxuria to de-repress HgbF gene
Since 97% of our circulating Hgb is alpha-1, what is the remaining 3%?
- 2% HgbA2 (2 alpha, 2 delta)
- 1% remaining HgbF
Red marrow
- hematogenous/active
- all bones in new born
- flat bones and vert. in adults
- ongoing hematopoeisis
Yellow marrow
- long bones of adults
- energy storage
- can convert to red marrow in times of stress
Where does marrow begin to form in an embryo?
- yolk sac (3rd or 4th week)
- then liver/spleen (until month 2)
- then bones when they are formed
What is the first bone to form in the body?
clavicle
Order of cell maturation in erythropoiesis
- pro erythroblast
- basophilic erythroblast
- polychromatic erythroblast
- Normoblast
- Erythrocyte
Proerythroblast stage of erythropoiesis
- arises from stem cell
- lg cell
- multiple nucleoli
- basophilic d/t ribosomes
- can divide
- Hgb synthesis begins
basophilic erythroblast stage of erythropoiesis
- shrinks
- blueish granules (basophilic)
- can divide once
- clock face
- Hgb increasing
polychromatophilic erythroblast stage of erythropoiesis
- shrinks further
- nucleus is 50% of cell
- enough Hgb formed to take on pink color over blue
- multiple divisions
Normoblast stage of erythropoiesis
- smaller still
- small/dense nucleus
- pyknotic nucleus stops division
- Hgb major protein in cytoplasm
Erythrocyte stage of erythropoiesis
- nucleus has extruded
- mature RBC
- 80% hgb
Mature RBC (erythrocyte) characteristics
- lives about 120 days
- 7.2 microns in diameter
- biconcave and flexible
Size variations of RBCs
- microcytes: <6 micron diameter
- macrocytes: >9 micron diameter
- hypochromic: not making enough Hgb, cells are small
Main causes of hypochromic microcytic anemia?
- Fe deficiency anemia
- lead poisoning
- anemia of chronic disease
- thalassemia
Howell-Jolly bodies
- retained DNA fragments found in disease states
- RBC w/ blue dot in it – indication of chronic disease
If the howell-jolly bodies are in a circular in formation, what is the condition?
- Cabot rings
- indication that a problem is present just not specific as to what
Erythrocyte maturation summary
- decreased cell volume
- decreased nuclear diameter leading to extrusion
- increase in cytoplasmic Hgb
- decrease in non-nuclear organelles
Platelets
- aka thrombocytes
- enucleated disklike cell fragments 2-3 micron in diameter
Platelets bud from what?
megakaryocytes in marrow
platelet membranes
- rich in GAGs and glycoprotein
- gives a sticky quality to adhere to exposed collagen
d/t the “stickiness” of platelet membranes, what do they bind to?
-vWF (von Willebrand Factor) outside of vessels
Contents of platelets as they bud off of megakaryocytes
- thromboplastin
- serotonin
- thrombostenin (contracts clots)
fxn of thromboplastin
- converts prothrombin to thrombin
- thrombin coverts fibrinogin to fibrin
platelet life span
- 7-10 days
- 10% are replaced daily -this is fairly high turnover so taken out of circulation in spleen
Effects of aspirin on platelets
- interferes w/ thromboplastin – this prevents fibrin formation and coagulation
- prolongs bleeding time
Return to normal after aspirin use
- have to replace 30% new platelets
- this is 3 days
- so technically you only need to take aspirin every 3 days, but adherence would be poor then
Granulocyte type luekocytes
- neutrophilic
- eosinophilic
- basophilic
Agranulocyte leucocytes
- lymphocytes
- monocytes
Other names for neutrophils
- Polymorphonuclear leukocytes
- Polymorphonuclear neutrophils
- Polys
- PMNs
- Segmented neutrophils
- Segs
WBC maturation in granulocyte series
- stem cell
- myeloblast
- promyeloblast - can develop into any of the 3 granulocytes
- myelocyte (eosinophilic, neutrophilic, basophilic)
- metamyelocyte
- stab cell
- completely differentiated cell
What point in granulocyte maturation divides the cells that are in marrow vs. circulation
- up to metamyelocyte = marrow
- stab cells on = circulation
significant of neutrophilic band cell count
- normal conditions: 4% band cells in circulation
- then nucleus condenses to form mature neutrophil
- infection: band count increases to 9% or higher
- only good indicator in pts who are not immunocompromised
What would a bone marrow biopsy look like in leukemia
- early stage cells are present in peripheral circulation
- no young RBCs
- classified by youngest cell present (i.e myeloblastic leukemia)
Neutrophilic lineage
- neutrophilic myelocyte: nucleus becomes eccentric and indented
- metamyelocyte: deeper indented nucleus; decrease in protein synth.; high glycogen storage
- band stage
If nuetrophilic bands are present at higher than 3-5%, what is it called?
-left shift
mature neutrophil
- 60-70% circulating WBCs
- 2-5 lobes linked w/ chromatin thread
- no nucleoli
- live 12-14 hrs in circ.
- live 1-4 days in con. tissue
“drumstick” on mature neutrophil
-inactivated X chromosome
Effect of epinephrine on seg count
- elevated ct but not d/t infection
- caused by demarginalization
main function of neutrophils
- phagocytosis
- of debri, bacteria, dead cells
- if migrate to tissues all at once and die = pus
Eosinophils
- myelocyte and metamyelocyte stages
- 2-4% of circulating WBCs
- bilobed nucleus
important enzyme in eosinophils
- peroxidase
- useful in killing protazoa
- also have factors that inhibit mast cell degranulation
increased eosinophils could indicate what things?
- allergies
- round worm infection
- bacterial myocarditis
basophils
- same myelocyte to metamyelocyte stages
- <1% of circulating WBCs
- irregular nucleus
- granuoles contain heparine and histamine
agranulocytes
- lymphocytes: B, T, and null
- monocytes
Percentages of lymphocytes
- T: 80%
- B: 15%
- null: 5%
CD8+
killer/cytotoxic T cells
CD4+
Helper T cells
how do immune cells recognize other somatic cells?
-through cell surface markers
primary markers are proteins of what?
-major histocompatibilty complex (MHC) = HLA (human leukocyte antigen)
HLA markers in relation to disease
- certain HLA markers tend towards certain disease states
- for ex: ankylosing spondylitis (HLA B27), DM type 1, hemochromotosis, Sjogren’s
- not the cause of disease but suggestive
Class I MHCs
found on all body cells except for B cells
Class II MHCs
found on B cells
Explain the process of how a cell becomes recognizable as self
- in embryo, circulating antigens are endocytoced
- then they are processed into fragments and reintroduced as MHCs
- the new MHCs are packaged into granules and returned to cell surface as self
Components of a T cell binding an antigen presenting cell
- T cell receptor binds the MHC containing Ag fragment
- the binding is stabilized by either CD4 or CD8
- if T cell binds to non self = rejection
clonal deletion
the removal of T and B cells that have receptors that recognize self before they are able to mature into immunocompetent lymphoctes
What are the steps in the process of clonal deletion?
- embryonic T cells have both CD4 and CD8 receptors
- in the thymus they are presented to thymic cells
- if embryonic T cell recognized self, have to delete it
- if it doesn’t recognize self, allow to enter circulation where it will lose of the the receptors and become specified as CD4 or CD8
What happens when the embyonic T cells that recognize self in the thymus are allowed to enter into circulation?
autoimmune disease
CD4 T cells bind to what?
class II MHC on B cells
B cell antibodies
- IgM
- IgA
-when Ag binds, they are indocytosed and returned as class II MHC
What is the relationship between CD4 T cells and B cells?
- T cell binds B cell and releases interleukins to cause proliferation of B cells
- B cells begin producing antibodies against the Ag attached to its MHC
- humoral immunity
Without CD4 T cells what is the out come?
- little or no B cell response
- loss of humoral immunity
When does HIV transition to AIDS?
- when CD4 count drops below 200
- can’t mount an immune rxn
CD8 T cells bind to what?
Class I MHC on all cells except for B cells
Action of CD8 T cells
- binds non self and injects perforin into cells causing contents to leak out and lysis
- cell mediated immunity
What all can activate ia CD8 (killer T cell)?
- non self Ag from infection
- another MHC from different “self” cell
- altered MHC from tumor
Monocyte
- not fully mature cell in circulation
- exists 8-12 hrs in circulation
- irregular horseshoe-shaped nucleus
when monocytes migrate into tissues, what do they become?
macrophages
Plasma cells
- originate as B cells
- not in circulation
- few in number except where bacteria and foreign proteins are
- clock faced nucleus
When activated by Ag, what do plasma cells secrete?
IgE
Function of IgE when produced by plasma cells
bind to mast cells which contain histamine, heparin, ECF-A (eosiniphil chemotactic factor of anaphylaxis) and SRS-A (slow-reacting substance of anaphylaxis)
What cells are abundant in openings to the environment? (mouth, nose, anus, etc.)
- monocytes
- plasma cells
