MA6 - Bone Marrow and Peripheral Blood Flashcards
What are the components of blood?
RBCs = erythrocytes
WBCs = leukocytes
platelets (suspended in plasma)
What is a complete blood count?
full blood count that includes parameters of RBCs
What is a differential?
relative number of each WBC in a blood sample
What is the percent composition of blood?
44% RBC
55% plasma
1% buffy coat (contains WBCs)
All cells of the blood are generated in
the bone marrow
Define hematocrit.
pakced volume of erythrocytes in a unit volume of blood
Define buffy coat. (2)
thin translucent layer above RBC layer
contains leukocytes
Describe the layers observed if you were to centrifuge a blood sample.
plasma on top
thin buffy coat in the middle
RBCs on the bottom
What is plasma?
yellowish fluid above buffy coat after blood separates in the presence of anticoagulants
What are the four primary components of plasma?
plasma proteins
electrolytes
nutrients and waste
water
What is serum?
straw-colored fluid phase when blood clots in the absence of anticoagulants
What are the three types of granulocytes?
neutrophils
eosinophils
basophils
What are the two types of agranulocytes?
monocytes
lymphocytes
Bone marrow fills what space?
between trabeculae in spongy bone
Describe the composition of bone marrow. (2)
highly branched vascular compartment of sinuses and an extravascular compartment (hematopoietic spaces)
What is the function of the hematopoietic space?
site of new blood cell development
Describe the structure of sinusoids in bone marrow.
sinusoids are highly branched with flat endothelial cells
Describe the movement of blood through bone marrow.
arteries @ diaphysis → percolates through marrow via venous sinuses → picks up new blood cells → central sinus → venous circulation
Differentiate between the components of RBCs that carry O2 and carry CO2.
globin portion of hemoglobin releases CO2
heme portion of hemoglobin binds O2
What stain gives RBCs a salmon pink color?
Giemsa & Wright stain
What is the advantage of RBCs’ biconcave shape?
facilitates gas exchange by affording a large surface area relative to its volume
What is the diameter of RBCs?
7-8 μm in diameter
Mature RBCs are unique in that they lack nuclei. Explain how the nucleation of RBCs change.
made in bone marrow as nucleated cells
then released into blood sinusoids of bone marrow after nucleus extrusion
Define reticulocyte.
red cells newly released from the bone marrow
Red cells newly released from the bone marrow are called
reticulocytes
What is the basis of the name “reticulocyte?”
because of a reticular (mesh-like) network of ribosomal RNA
Reticulocytes comprise what portion of the total erythrocyte count?
reticulocytes constitute 1-2% of total erythrocyte count
At what point do reticulocytes become mature RBCs?
during passage through the spleen
What is the lifetime of an RBC?
4 months, then gets degraded by the spleen
What are RBC “flexibility tests” and why are they important? (2)
RBCs have to change shape when squeezing through narrow capillaries
so each time RBC passes through spleen, it undergoes a flexibility test and if it fails, it is destroyed
(T/F) RBCs have a cytoskeleton.
False
What feature of an RBC allows it to pass through a narrow structure and preserve its shape?
RBCs have unique variant of membrane skeleton underlying plasma membrane which provides flexibility and stability, allowing RBCs to return to concave shape
Define anisocytosis.
abnormal deviation in RBC size
What are the two types of anisocytosis?
microcyte/microcytosis
macrocyte/macrocytosis
Define microcyte.
RBC smaller than 6 μm
Define macrocyte.
RBC larger than 9 μm
What is poikilocytosis?
abnormal deviation in RBC shape
(T/F) pH can alter RBC morphology.
True
Define spherocyte.
sphere-shaped RBC
Define elliptocyte.
elongated RBC
Hereditary spherocytosis results from
defects in:
ankyrin
spectrin
band 3
Define ankyrin.
protein that anchors the membrane skeleton to the plasma membrane
Define spectrin.
long, highly flexible cytoskeletal protein of the membrane skeleton
Define band 3.
Cl-/HCO3- anion exchanger
Hereditary elliptocytosis results from
defects in:
spectrin
band 4.1
Define band 4.1.
part of membrane skeleton of red cells
Define chromasia.
differences in staining intensity, which sometimes indicate various pathologic conditions
Define anemia.
condition when hemoglobin is not present in sufficient amounts
Define thalassemia.
results from reductions in globin chain synthesis
Differentiate between alpha and beta thalassemia.
alpha thalassemia = synthesis of hemoglobin alpha chains impaired
beta thalassemia = synthesis of hemoglobin beta chains impaired
What is the ratio of WBC to RBC?
1:700
Define diapedesis.
extravasation of a leukocyte across the endothelium into the surrounding tissue
Differentiate between how RBCs and WBCs function in the bloodstream.
unlike RBCs, the WBCs do not function within the bloodstream but rather use it as a means to travel to various parts of the body
How do WBCs enter their target tissue?
via diapedesis
WBCs are classified into what two groups?
granulocytes
agranulocytes
Define granulocytes.
cells that contain specific granules, which in turn contain proteins and enzymes that perform cell-specific functions
Define agranulocytes.
lack specific granules
What is a feature common to granulocytes and agranulocytes?
both possess nonspecific azurophilic granules, which are lysosomes
Describe the general features of granulocytes. (5)
multi-lobed nucleus
abundant lysosomes = primary granules
10-12 um in diameter
arise in bone marrow from same progenitor cell
terminally differentiated = incapable of cell division
What is the general function of neutrophils?
first line of defense against bacterial infection
What percent of WBCs is made up of neutrophils?
55-60%
What is the defining morphology of neutrophils?
highly segmented nuclei
Rank the WBCs in order of abundance.
N > L > M > E > B
neutrophils > lymphocytes > monocytes > eosinophils > basophils
[mnemonic: Never Let Monkeys Eat Bananas]
Describe the distinguishing feature of female neutrophils.
contain Barr bodies, which are inactivated X chromosomes
What are the three types of granules found in neutrophil cytoplasms?
primary/non-specific granules (azurophilic)
secondary/specific granules
tertiary granules
Describe the composition of primary/non-specific granules in neutrophils.
lysosomes containing:
hydrolases
myeloperoxidases
lysozymes
elastases
What is the largest granule found in neutrophils?
primary/non-specific azurophilic granules
Describe how primary/non-specific granules of neutrophils appear in EM.
heterogeneous
Describe the composition of secondary/specific granules.
contain enzymes that assist neutrophil w/ antimicrobial functions
Describe how secondary/specific granules appear under EM.
heterogeneous in size
Describe the composition of tertiary granules.
contain phosphatases (gelatinases) and metalloproteinases (collagenases) which facilitate migration of neutrophil into/through connective tissue
Describe how tertiary granules appear under EM.
heterogeneous in size/shape
What is a band cell?
developing neutrophil at stage immediately preceding mature, segmented form
What are the seven events of extravasation?
leukocyte in blood vessel
capture
rolling
slow rolling
firm adhesion
early transmigration
transmigration
LCRSFET (Laura Chapman rode San Francisco’s E train)
Describe the rolling step of extravasation.
selectins on endothelial cells bind to selectin ligands on neutrophils → neutrophils adhere to endothelial lining (a.k.a. margination)
Define margination.
process by which leukocytes associate with endothelium prior to diapedesis
Describe the activation and firm adhesion steps of extravasation. (2)
integrins of neutrophils bind to endothelial cellular adhesion molecules
chemokines trigger neutrophil arrest by increasing integrin affinity (firm adhesion)
Describe the transmigration step of extravasation.
histamine + heparin at injury site released by perivascular mast cells
loosening of endothelial cell junction
gelatinases degrade basal lamina
neutrophils cross through (diapedesis)
Define chemotaxis.
directed migration of neutrophils through tissues to injury site in response to chemokine gradients
Define phagocytosis.
actin-dependent process of engulfment for large extracellular species
What is the ultimate fate of foreign particles engulfed by phagosomes?
fusion of phagosomes + specific/azurophilic granules = phagolysosomes in which species is killed via oxidative (ROS) or non-oxidative means
After neutrophils perform their functions, they die. What forms as a result of their death?
pus: accumulation of dead leukocytes + bacteria + tissue fluid
What are the two general functions of eosinophils?
kill parasites
modulate allergic inflammatory responses
What is the morphology of eosinophils?
bi-lobed nuclei w/ sausage-shaped lobes
Describe the contents of eosinophils. (3)
large specific granules that contain:
major basic protein
eosinophilic cationic protein
eosinophil-derived neurotoxin
What is the function of the basic and cationic proteins present in eosinophils?
help combat larger parasites
(T/F) Eosinophils have azurophilic granules.
True, but they are usually obscured by the larger specific granules
Eosinophilic chemotactic factors are released by what cells? (3)
mast cells
basophils
neutrophils
Describe how eosinophils carry out their anti-parasite activity.
degranulate their basic and/or cationic protein on surface of parasite, forming pores in pellicles through which ROS can enter the parasite and kill it
What are the general functions of basophils?
defend against parasite invasions
participate in allergic responses
What is the abundance of basophils?
less than 0.5% of WBCs
What is the morphology of basophils?
bi-lobed nucleus [not easily visualized]
large specific granules that stain dark blue above nucleus
azurophilic granules [not visible]
What are the contents of the granules of basophils?
heparin
histamine
eosinophil chemotactic factor
neutrophil chemotactic factor
peroxidase
[HHENP]
Describe how basophils carry out their function.
allergens cause basophil to release contents into extracellular space (similar mechanism to mast cells)
Histamine is contained in which leukocyte?
basophils
The release of histamine by basophils causes (3)
constriction of bronchial smooth muscle
vasodilation of capillaries and arterioles
result: drop in blood pressure
What is anaphylactic shock?
second exposure to same allergen causes intense generalized response in which large numbers of basophils + mast cells are degranulating
What is the effect of anaphylactic shock?
large-scale degranulation of basophils and mast cells results in hypotension due to (1) bronchial smooth muscle constriction and (2) vasodilation of capillaries and arterioles
What are the two agranulocytes?
monocytes
lymphocytes
What are monocytes?
phagocytic cells that stay in circulation for a few days before entering tissue to differentiate into macrophages
What is the largest (in terms of size) leukocyte?
monocytes
What is the abundance of monocytes?
make up 3-8% of WBCs
Give three examples of context-specific macrophages.
histiocyte = resident connective tissue macrophage
Kupffer cell = macrophage resident in liver sinusoids
dust cell = alveolar macrophage of lung
Describe the granule content of monocytes.
have azurophilic granules
lack specific granules (thus why they’re called agranulocytes)
Describe the morphology of the monocyte.
single-lobed nucleus w/ horseshoe shape
What are the functions of monocytes that have differentiated into macrophages?
phagocytose old erythrocytes in spleen
phagocytose/destroy bacteria
phagocytose apoptotic bodies
produce cytokines that activate inflammatory responses
serve as part of mononuclear phagocyte system
What are lymphocytes?
cells that serve as part of the immune system and protect against pathogens
What is the relative abundance of lymphocytes?
make up 30% of WBCs
What are the two types of lymphocytes?
T lymphocytes
B lymphocytes
Describe the features of T lymphocytes. (3)
small
quiescent
cell-mediated adaptive immunity
Describe the features of B lymphocytes. (4)
small
quiescent
humoral immunity
can differentiate into plasma cells that produce antibodies
What is the relative abundance of T and B lymphocytes?
80% of lymphocytes are T and 15% are B
What is the morphology of lymphocytes?
small ring of light blue cytoplasm around nucleus
What is the diameter/size of lymphocytes?
in the blood = 8-10 um (only slightly larger than an RBC)
medium/large = 12-18 um
What are natural killer cells?
a.k.a. large granular lymphocytes
large lymphocytes important in the innate immune system that have anti-tumor and anti-viral activities
What are the general functions of platelets/thrombocytes? (2)
adhesiveness and aggregation to temporarily seal blood vessels
initiate local coagulation (blood clotting) in response to injury
Platelets are derived from
megakaryocytes, a type of cell in the bone marrow
What is the size of plateles?
2-3 um in diameter
Describe the morphology/composition of platelets
hyalomere = peripheral ring rich in cytoskeleton
granulomere = central darker region w/ other organelles
What is the lifespan of a platelet?
less than 14 days
What is the sequence of events for platelet function? (8)
at injury, platelets release contents of granules → platelets adhere to each other = platelet activation → prothrombin converted to thrombin → thrombin facilitates platelet aggregation → fibrinogen converted to fibrin → formation of blood clot = thrombus → clot contracts to close off injured epithelium → endothelial cells release plasminogen activators during/after repair to dissolve clot
What is a thromboembolism?
blockage (embolism) of blood vessel by piece of a thrombus (blood clot) carried by circulation system
What is thrombocytopenia?
deficiency in number of platelets in circulation
What are the symptoms of thrombocytopenia?
bleeding from small vessels occurs, leading to purplish splotches on skin
