Blood/Hemopoiesis Flashcards
what constitutes blood?
formed elements (cells) + plasma
what does plasma contain?
- water
- proteins (fibrinogen, albumin, globulins)
- solutes
how many erythrocytes are contained in an individual’s peripheral blood?
25 trillion
what percent of total blood volume do RBCs make up?
45%
describe RBCs
- biconcave w/ no nucleus or organelles
- stain eosinophilic
- 1/3 of mass = Hb
- lifespan of 120 days
where are RBCs destroyed?
spleen, liver, bone marrow
what are reticulocytes?
new RBCs from bone marrow - complete Hb synthesis and mature 1-2 days after entering circulation
sickle cell anemia
genetic alteration in the Hb beta-chain (single aa substitution Val -> Glu) -> altered HbS denatures and clusters band3 protein, ankyrin and spectrin
- stuck in splenic sinuses, removed by macrophages
- adhere to capillary endothelial cells -> occlusion
- enlarged spleen
- short life span
hereditary spherocytosis
inherited defects in RBC membrane - spheroidal, less deformable cells
- SPECTRIN DEFICIENCY
- some have ankyrin mutation
- cells lack central pale zone in blood smears
- patients have anemia and splenomegaly
what produces RBC biconcave shape and allows cells to change shape?
spectrin in association w/ ankyrin and actin
what does the inability to alter shape of spherocytes result in?
sequestration in the splenic cords and failure to pass into splenic sinuses -> enables destruction by macrophages
what are platelets?
cell fragments 2-5um in diamater derived from megakaryocytes
what do megakaryocytes have that are connected to extracellular space?
platelet demarcation channels derived from plasma membrane
what is the function of platelets?
- blood clotting
- clot retraction
- clot dissolution
what do platelets contain?
- alpha granules
- dense core granules
- numerous cytoplasmic microtubules
- vasoactive compounds (TXA2 derived via cyclooxygenase metabolism)
describe alpha granules of platelets
lysosomal
describe dense core granules of platelets
contain serotonin, ADP, ATP, calcium
what happens to platelets upon activation?
platelets change from their discoid shape to more flattened appearance w/ extensive ruffling of cell membrane -> associated w/ rearrangements of cytoskeleton -> microtubule redistribution and rapid polymerization of actin into microfilaments
describe neutrophils
- granulocytes 9-12um in diameter
- 3-5 lobed nucleus
- terminally differentiated (no mitosis)
- specific granules
describe the specific granules of neutrophils
- small: alkaline phosphatase, phagocytins
- large: azurophilic granules w/ myeloperoxidase and lysosomal enzymes
what is the first phagocytic cell to appear during inflammation?
neutrophil
what percentage of WBCs are neutrophils?
65-75%
what are immature neutrophils?
stab/band cells - horseshoe nucleus
- live 6-10 hours in blood and 2-3 days in tissue
- banding due to neutrophils in different stages of differentiation
describe basophils
granulocytes 10-12um in diameter
- low numbers in blood (0.5-2% of WBCs)
- contain large basophilic granules
- lobed nucleus (hard to see due to granules)
- lives 1-10 hours in blood
what do the large basophilic granules of basophils contain?
- hydrolytic enzymes
- histamine
- heparan sulfate proteoglycan
- slow reacting substance
what do the basophilic granules of basophils secrete?
eosinphil chemotactic factor
what do basophils bind?
IgE (like mast cells)
describe eosinophils
granulocytes 12-15um in diamater
- 0-4% of WBCs
- large eosinophilic granules
- bilobed nucleus
- leave bloodstream and enter CT -> increased #s in allergic reactions and parasitic infections
what do the large eosinophilic granules of eosinophils contain?
- arylsulfatase
- histaminase
- acid phosphatase
- ribonuclease
- peroxidase
function of histaminase
decreases severity of allergic reaction
describe monocytes
agranular phagocytic leukocytes - 20-25 um diam (BIG)
- 2-9% of WBCS
- live 1-3 days in blood
- reniform nucleus
- lysosomes
what happens to monocytes when they moves from blood into tissue spaces?
differentiate into other cells in monocyte/macrophage lineage:
- macrophage
- osteoclast
- giant cells
what are monocytes important for?
- regulation of immune response
- inflammation
describe lymphocytes
small, medium, and large mononuclear cells
- 20-35% of WBCs
- round/oval nucleus in small cells
- reniform nucleus in large cells
- VERY LITTLE CYTOPLASM
where are T and B lymphocytes derived from?
T: derived from bone marrow, mature in thymus
B: derived from bone marrow lymphoid progenitor cells
what are large granular lymphocytes?
null cells - may differentiate into natural killer or killer cells
describe T cell vs. B cell projections
T cells generally have fewer surface projections than B cells
describe bone marrow in the fetus
it is an actively hematopoietic tissue
describe adult bone marrow
less hematopoietic than fetal b/c it regresses from hematopoietic red marrow to resting, fat-storing yellow marrow
where is red marrow still present in the adult?
- vertebrae
- sternum
- ribs
- skull
- pelvis
- proximal femur
where is bone marrow typically taken from?
iliac crest
when does hematopoiesis begin?
early in embryonic development:
- second week of gestation in yolk sac
- 6th week in liver
what is differentiation of bone marrow progenitor cells stimulated by?
various cytokines that are colony-stimulating factors (CSFs)
- interleukin-7 (lymphoid precursors-B/T cells)
- granulocyte-monocyte CSF
- monocyte CSF
- granulocyte CSF
what do myeloid and lymphoid progenitor cells give rise to, respectively?
lymphoid: gives rise to lymphocyte cells
myeloid: everything else in blood
function of erythropoietin and where does it come from?
from kidney -> causes CFU-E cells to differentiate into erythroblasts
what is the order of erythrocyte differentiation?
erythroblast -> basophilic erythroblast -> polychromatophilic erythroblast -> orthochromatic erythroblast
when is the developing cell a basophilic erythroblast?
when ribosomes accumulate in the cytoplasm, increasing erythroblast basophilia
when is the developing cell a polychromatophilic erythroblast?
when ribosomes bind Hb mRNA, synthesize Hb -> reduces the cell’s basophilia
when is the developing cell an orthochromatic erythroblast?
when [Hb] increases, causing cytoplasm to stain pink
also called normoblast
what happens once the cell starts accumulating Hb as an orthochromatic erythroblast?
- nucleus condenses, undergoes heterochromatic involution
- cell sheds nucleus and most mitochondria and polyribosomes -> forms an erythrocyte
what happens to the Hb from destroyed RBCs?
Hb degrades into:
- bilirubin and other materials, which are excreted in bile
- iron, which is transported by serum glycoprotein transferrin to bone marrow to make to synthesize new Hb
relationship of reticulocyte vs. polychromatophilic erythroblast?
reticulocyte is more mature version of polychromatophilic erythroblast
what is granulopoiesis?
when granulocytes develop from CFU-S cells
what is the first recognizable granulocyte precursor in granulopoiesis?
myeloblast - large euchromatic nucleus with several nucleoli and no granules in a basophilic cytoplasm
what does the myeloblast turn into?
becomes promyelocyte when the cytoplasm accumulates a few azurophilic (nonspecific) granules
- nucleus accumulates heterochromatin
- slight indentation occurs in nucleus
describe promyelocyte differentiation
begins as neutrophilic, eosinophilic, or basophilic specific granules accumulate in cytoplasm and nucleus continues to condense and lobulate
what is a metamyelocyte?
has accumulated many specific granules but has yet to complete the process of nuclear condensation and lobulation
describe monopoiesis
monocytes develop from same CFU-S cells as granulocytes
-but there is a different developmental process that includes monoblast and promonocyte stages
describe lymphopoiesis
lymphocytes develop from lymphoblasts, which are derived from CFU-Ly cells
what are megakaryoblasts?
differentiated CFU-S cells
what induces differentiation of megakaryoblasts into megakaryocytes?
thrombopoietin
describe megakaryocytes
- only exist in bone marrow
- multilobulated
- do not divide but become larger w/ nucleus -> polyploid (endomitosis)
describe release of platelets from megakaryocytes
slowly release small cytoplasmic fragments into the bloodstream in the bone marrow vascular channels
when do the megakaryocytes fragment?
when the cell plasma membrane fuses w/ sER membranes
how long do platelets remain in bloodstream?
7-10 days
acute lymphocytic leukemia (ALL)
- rapid growth of immature WBCs
- common in children
acute myelogenous leukemia (AML)
- unregulated growth of WBCs from myeloid lineage
- common in adults
chronic lymphocytic leukemia (CLL)
- B cell cancer
- mainly in adult males
chronic myelogenous leukemis (CML)
- unregulated growth of myeloid cells (neutrophils, eosinophils, basophils) in bone marrow
- translocation b/w chromosome 9 and 22 (philadelphia chromosome/translocation)
