Mar19 M3-Hematopoiesis and Leukemias Flashcards
blood centrifuge components
supernatant = plasma (serum = plasma without clotting factors)
buffy coat = WBCs and platelets
bottom = RBCs
hematocrit def
% of blood volume that is RBCs (normal 45%)
RBC content and what it doesn’t contain
membrane, cytoskel, enzymes, Hb
NO NUCLEUS NO ORGANELLES
why males a bit more RBCs
testosterone has a trophic effect on the BM
RBC turnover
110 days lifespan. 1% replaced daily. broken in liver and spleen
anemia def
men: Hb below 140
women: Hb below 120
cytoskeletal and Hb disorders of RBC + consequence of these
cytoskeletal: spherocytes, elliptical
Hb disorders: sickle cell, thalassemia
*cells are lysed more. fragile and rupture.
proteins in RBC cytoskeleton
- ankyrins (bind membrane and other cytosk elements)
- spectrin (between ankyrins)
- band3 (sticks out of cell)
normal blood smear
- mainly RBCs
- all RBCs regular and look the same
normal RBC size and volume
size normal: 7-7.5 um
volume: 80-100 fL
microcytosis cause
- Fe deficiency
- Hb disorders (like thalassemia)
- lead poisoning
macrocytosis cause
- B12 deficiency
- thyroid disease
- drugs (methatrexate for rheumathoid arthritis and hydroxyuria in chemo) and alcohol
- marrow problem (myelodysplasia)
red cell fragments meaning
severe disorders (sepsis, DIC, TTP)
eccinocytes (spiky cells)t and target cells (codocytes, look like bullets) meaning
eccinocytes = renal insufficiency
target cells = hepatic insufficiency
sicke cell pathophgy
mutation of beta chain on 6th residue. Hb cristalizes. cell has sickle shape and plugs circulation. small ischemic events
reticulocytes def
almost mature RBCs in blood that still have nuclear content for 1-2 days
reticulocyte count use
- anemia with HIGH reticulocyte count = BM is functioning (hemolytic anemia, bleeding)
- anemia with LOW reticulocyte count = BM problem (lack Fe, drug suppresses it, lack stimulus)
anemia with reticulocyte count that is normal
NOT a normal thing.
indicates BM issue
platelet main fct and things that help it
clotting. has 5HT for vessel constriction. TX. proteins on membrane to enable interaction with platelets and clotting factors + send pseudopodes to bind other platelets
platelets origin
cells called megakaryocytes (cyto doesn’t divide, nucleus only so nuclear content x64)
studies if low blood platelets
megakaryocyte count.
high = problem with platelets in circulation (drained)
low = BM problem
2 subtypes of WBCs
granulocytes (polymorphonuclear), short lived: N, B, E
agranulocytes (mononuclear), variable lifespans: monocytes, lymphocytes
barr body in neutrophils
In females, is the condensed X chromosome pushed on the side
2 kinds of neutrophil granules
- primary (AP, collagenase, lactoferin, lysozyme)
- azurophilic (collagenase, lysozyme, cathepsin, myeloperoxidase, 5’ nucleotidase, etc.): visible kind
neutrophil fct
major effector of immune system. phagocytosis. phagosome fuses with lysosome: phagolysosome
eosinophil on EM
granules with large crystals. contain major basic protein.
they surround parasites and release these
basophil granules content + their function
- heparin, histamine, leukotriene
- role in hypersensitivity rxs
WBC that can do mitosis
monocytes
monocyte fct
become macrophages (in tissues) after spending 10-120 HOURS in the blood. phagocytosis + present (APCs) epitopes to immune cells
atypical lymphocytes on microscopy + means what
-active, expanding cytoplasm
-heavy blue staining edges
-open chromatin
VIRAL INFECTIONS: INFLUENZA, INFECTIOUS MONO
where hematopoiesis happens
yolk sac - liver - spleen - bone marrow
in children, distal long bones + axial skeleton
in adults, mainly axial skeleton
2 types of BM
red (hematogenous): color produced by blood and blood-forming cells
yellow BM: color produced by presence of adipose cells
how BM types vary with age
more yellow and less red with age
100-age is amount of red
key players in hematopoiesis
- HSC
- pluripotent stem cells (derived from HSC)
- stroma (endothelial cells, fibroblastoid cells, GF production)
- microenvironment
- distal cytokines
substances acting on the bone marrow + on what cells
- growth factors
- cytokines (IL-1, 3, 6 and 11, SCF, G-CSF)
- act on HSCs and pluripotent stem cells
proportions of cells in BM
-HSC less 0.2%
-pluripotent SC a bit more
-mostly erythrocytes, platelets, leukocytes, myeloid and lymphoid cells.
(+ MICRO ENVIRONMENT: stromal cells which are macrophages, fibroblasts and endothelial cells)
HSC charact
- self-renewable (so does symmetrical and asymmetrical replication)
- CD34 and Sca-1 markers
- used in stem cell transplantation
progenitor cells charact
- cells not capable of indefinite self renewal
- may not be able to diff in all cell types
marrow progenitor cells charact
- can diff in all blood cells
- can’t renew indefinitely
commond myeloid progenitor cells include what 2 cell types
- common megakaryocyte and erythroid progenitor
- common granulocyte (meaning ‘‘phils’’) and monocyte progenitor
hematopoiesis 1st cell category and the cells
Stem cells (1. long term HSC 2. short terms HSC comes from lt-HSC)
hematopoiesis 2nd cell category and the cells
Progenitor cells
- MPP (multipotent progenitors or pluripotent ..), comes from st-HSC
- CMP and CLP come from MPP
- MEP and GMP (come from CMP)
what type of cells in hematopoiesis after progenitor cells
committed precursor cells
1. cells that come from MEP, GMP and CLP. one for each blood cell that will be created
cell type after committed precursor cells in hematopoiesis
- 2 committed precursor cells from MEP give megakaryocyte and RBCs
- 5 committed precursor cells from GMP give mast cells, the 3 phils, monocytes
- 3 committed precursor cells from CLP give T cells, B cells and NK cells
what regulates hematopoiesis
- genetics
- soluble signals from neighboring cells
- messages sent from rest of the body
erythropoiesis 6 stages and length
56 days. nuclei get smaller and more condensed at each stage
- proerythroblast
- basophilic normoblast
- polychromatic normoblast
- orthochromatic normoblast
- reticulocyte
- RBC
regulation of erythropoiesis
O2 sensors in the kidney. low O2 = kidneys make EPO (erythropoietin).
regulation of thrombopoiesis
- TPO (thrombopoietin) made by the liver is the megakaryocytic GF
- see thrombocytopenia in cirrhosis
regulation of WBCs production
molecules from
- BM blood and stromal cells
- blood
- outside (drugs that stim WBC growth)
