Blood and Hematopoiesis Flashcards
Hematopoiesis
Process of blood cell development
Hematopoietic tissues
Fetus- liver is primary site, with some occurring in the thymus, spleen, and lymph nodes;
Infancy through adulthood- bone marrow is primary site; If marrow is compromised can make blood cells in liver, spleen and nodes again.
Formed element
RBCs, WBCs, platelets
Formed elements of blood
%
%RBCs (aka hematocrit): 3 times hemoglobin males=41-53 %; females=36-46% %WBCs: 1% %Plasma: 49-64%
Characteristics of plasma
liquid extracellular component. 90% water, 7% protein, .9% inorganic ions, remaining: nutrients, blood gases, hormones
Major plasma proteins
Albumin (increases osmotic pressure, protein carrier, most abundant),
Globulin (alpha/beta: protein carriers, clotting factors, lipoproteins. gamma: immunoglobulins)
Fibrinogen and Prothrombin (clot formation)
Serum
Clear yellow supernatant remaining after blood coagulates and centrifuge
Contains factors released from platelets and most of the components of plasma except: clotting factors, platelets, cells.
Erythrocytes
Red blood cell, bi-concave, non-nucleated, contains hemoglobin
Macrocyte
RBC > 9 micrometers diameter.
Low levels of B12 and folate interfere with DNA synthesis, cellular formation takes longer, but hemoglobin synthesis kept going.
Microcyte
RBC:
Reticulocyte
Immature RBC that has entered circulation.
1-2% of RBCs in circulation, still has some RNA which stains as blue aggregations
Concentration of RBCs in blood of adult male/female
Male:41-53%
Female: 36-46%
RBC life span and function
Lifespan: ~120 days
Function: transport O2 to tissues and carry CO2 away
Major classes and types of leukocytes, lifespan, and %
Granulocytes: Neutrophils- 50-70% of leukocytes in circulation; lifespan of 1-4 days Eosinophils- 1-3%; 6 days Basophils- less than 0.3%; 1-2 days Agranulocytes: Monocytes: 2-8 %; \_\_\_ days Lymphocytes: 18-42%; \_\_\_\_ days
Types of cells associated with each class of leukocyte and their function
Neutrophils: Formed in bone marrow, stored in medullary, live in CT before dying by apoptosis, phagocytize bacteria and small particles in tissue. First responders to inflammation & infection.
Eosinophils: epithelia tissue of bronchi, GI tract, uterus, and vagina. Down regulators in allergic reactions, produce histamine and arylsulfatase to break down histamine and leukotrienes released by other cells. Indicates helminth infection (peroxidases to kill worm)
Basophils: release heparin, histamine, peroxidase, leukotrienes, and eosinophilic chemotactic factor. Become mast cells when they enter CT. Elicit allergic symptoms
Lymphocyte: T cells, B cells, involved in humoral immunity and the precursors to plasma cells, which form antibodies. Natural killer cells (kill virus infected cells & some tumor cells
Monocyte: precursor for mononuclear phagocytotic system, when they enter CT, they become macrophages
Concentration of leukocytes/microliter blood
Neutrophils: 1800-7700/ microliter blood Eosinophils: 600/microliter blood Basophils: 200/microliter blood Lymphocyte: 1000-4800/microliter blood Monocyte: 900/microliter blood
Relationship between leukocytes and connective tissue
Neutrophils: Live in CT for 1-4 days before before apoptosis
Eosinophils:
Basophils: Become mast cells when they enter CT
Lymphocytes:
Monocytes: precursor cells for mononuclear phagocytotic system, and become macrophages when the enter CT
Compartments a neutrophil passes through during maturation
Formed in red bone marrow in medullary cavity, undergo mitosis in mitotic compartment (3 days), progress to maturations compartment (4 days) while they finish developing. Fully matured they are moved to medullary storage where they can be released in large numbers if needed.
Origin and role of band neutrophils
Immature granulocytes, indicate infection when elevated in the blood. Bands are in the development stage following a metamyelocyte and have a curved, elongated nucleus.
Function of Eosinophils
Surround parasitic worms (granules containing major basic protein, cationic protein, and peroxidase kills worms)
Down-regulate inflammation (histamines and arylsulfatase granules inactivate histamine and leukotrienes, phagocytose antigen-antibody complexes)
Conditions under which eosinophil numbers increase
Allergic reaction, helminthic/parasitic infection
Two major classes of lymphocytes and the ways in which they are distinguished
T cells: 60-80% of lymphocytes, originate in bone marrow, mature in thymus, DNA rearrangement confers antigen diversity, circulate among secondary lymphatic tissues, cell mediated immunity, helper T cells activate B cells
B cells: 20-30%, originate and mature in bone marrow, DNA rearrangement confers antigen diversity, circulate via lymph and blood, humoral (fluid based) immunity, activated by specific antigen AND helper T cell, precursor to plasma cells
Lymphocytes
Life span: Days during acute infections; up to years/decades for some plasma cells
Frequency: 18-42% of leukocytes
Structure: Small (90%) 6-8 microns, nucleus: spherical w/condensed and clumped chromatin, cytoplasm: thin rim; Medium/Large (10%) 9-8 microns, nucleus: larger, less condensed, cytoplasm: more
Function: adaptive immune response
Monocytes
Life span: In blood about 3 days
Frequency: 2-8% of leukocytes; 900/microliter blood
Structure: 12-20 microns, nucleus: oval/kidney shaped, chromatin: less condensed, delicate, cytoplasm: basophils (due to ribosomes)
Function: Innate and adaptive bacterial phagocytosis, wound healing, bone resorption, debris removal
Major contents of specific granules of neutrophils
small, near the limit of resolution of light microscope, alkaline phosphates, collegians, lactoferrin, lysozyme, several nonenzymatic antibacterial basic proteins
Major contents of specific granules of eosinophils
Course, eosinophilic, do not overlie nucleus, cystalline core seen by TEM (results in high refractivity)
Contents: Acid phosphatase, cathepsin, RNase, Eosinophil cationic protein, Arylsulfatase, Collagenase, Eosinophilic peroxidase, Major basic protein, B-Glucuronidase, Phospholipase, Histaminase, Major basic protein
Major contents of specific granules of basophils
Eosinophillic chemotactic factor, heparin, histamine, peroxidase, leukotrienes
Function similar to mast cell allergic responses
Bind IgE antibodies for allergen specific
Myeloid Tissue (NONE)
Biologic tissue with the ability to perform hematopoiesis mainly found as the red marrow in bones and can also be in the liver and spleen in fetuses
Lymphoid tissues (NONE) (Also see diagram of primary lineages)
tissues with lymphocytes
Primary/ Central lymphoid tissue: Sites of antigen independent lymphocyte generation, Bone marrow for B cells, Bone marrow and thymus for T cells
Secondary/ Peripheral lymphoid tissues: Where adaptive immune responses are initiated and lymphatic vessels that connect them to other tissues and bloodstream
MALT
GALT
BALT
CALT
Mucosa-associated lymphoid tissue
Gut-associated lymphoid tissue
Bronchus-associated lymphoid tissue
Conjunctiva-associated lymphoid tissue
Process of blood cell renewal (NONE)
· RBC’s are turned over every 120 days
· Macrophages of spleen, bone marrow, liver ingest old RBC’s.
· Globin portion is hydrolyzed into amino acids and excreted by kidneys in urine
· Fe molecules are reused by the body. Complexed in ferritin and hemosiderin.
· The rest of heme is degraded to bilirubin, transported to the liver and excreted in bile via the gallbladder. (Its ultimate fate is poop!)
Compare changes in hematopeoietic tissue types during embryonic and fetal stages, birth and adulthood
● 0-3 months: Hamatopoesis occurs in the yolk sac.
● After 7 weeks gestation: the liver takes over. It is the primary genesis site until 24 wks gestation.
● From 9 weeks: hematopoiesis is also seen in the lymph tissue and thymus.
● Hematopoietic cells are first seen in the red bone marrow at 10-11 wks. This is the primary site of erythropoiesis in the developing infant and adult.
● In adults, most of red bone marrow becomes fatty yellow marrow. Red marrow remains (and is the only site of erythropoesis) in the skull, vertebrae, ribs, sternum, ilia and proximal epiphyses of some long bones. It’s also the primary site of lymhopoeisis.
● In response to sustained blood loss, yellow bone marrow can convert back into red.
Pluripotential Stem Cell
- -self-renewal
- -can differentiate into almost any cell;
- -low mitotic activity
- -few bone marrow, fewer in blood
Multi potential stem cell
- -self-renewal
- -can give rise to many cells, but more limited than pluripotent;
- -low mitotic activity
- -few in bone marrow, fewer in blood
Progenitor cell
- -self-renewal
- -mono- or bi-potential
- -high mitotic activity
- -bone marrow»_space;> thymus/nodes/spleen/other lymphoid and proliferate
- -no mature fxn
Precursor cell
- -no self-renewal
- -no self-renewal
- -mono-potential
- -high mitotic activity
- -specific morphology and fxn
Colony forming cell
–stem cells; colony forming unit allows quantification of number of cells
Neutrophil (S, P, P)
Stem cell: myeloid
Progenitor: promyelocyte
Precursor: metamyelocyte and band neutrophil
Lymphocyte (S,P,P)
Stem cell: lymphoid
Progenitor: B or T lymphoblast
Precursor: Prolymphocyte/plasmacyte
Monocyte (S,P,P)
Stem cell: myeloid
Progenitor: myeloblast
Precursor: Promonocyte
Eosinophil (S,P,P)
Stem cell: myeloid
Progenitor: pro-melocyte
Precursor: metamyelocyte
Basophil (S,P,P)
Stem cell: myeloid
Progenitor: promyelocyte
Precursor: metamyelocyte
Platelet (S,P,P)
Stem cell: myeloid
Progenitor:
Precursor: Megakaryocyte
Erythrocyte (S,P,P)
Stem cell: myeloid
Progenitor: proeryhtroblast
Precursor: Reticulocyte
Erythropoiesis
Controlled by the release of erythropoietin released by the kidney
More erythropoietin released, the more RBCs are generated
Responds to low oxygen levels to increase RBC production
Erythropoiesis Stages (NONE)
Common myeloid progenitor cells in red bone marrow differentiate to form an erythroid colony forming unit made of pro-erythroblasts
Pro-erythroblasts - basophilic erythroblast -polychromatophilic erythroblast - orthorchromatophilic erythroblast (can no longer undergo mitosis) - reticulocyte (no more nucleus) - erythrocyte (loses ribosomes and enters blood stream)
As cells mature:
○ Cell size decreases
○ Lifespan increases
○ Chromatin condenses
○ Nucleus gets smaller until it is removed from cell
○ mRNA decreases
○ Hemoglobin increases
○ Cell goes from more basophilic (lots of RNA) to eosinophilic (lots of hemoglobin)
Granulopoiesis (NONE)
Begins with bone marrow pluripotent stem cell - myeloid stem cell - progenitor
All cells follow the same process to differentiation, the specific morphologic distinction between the different cell types is the appearance of specific granules in the myelocyte
Cells decrease in size, chromatin condenses, and nucleus changes shape from round to stated (indented) to band to segmented.
Granulopoiesis stages(NONE)
Begin: progenitor
1: Myeloblast
2: Promyelocyte
3: Myelocyte (different granule - different btw. eosinophil, basophil, neutrophil
4: Metamyelocyte
5: Eosinophil, Basophil, Neutrophil
Maturation of Lymphocytes
Essential recognition cells in specific immune defenses
◆ Lymphoid stem cell line origin is called lymphopoiesis.
◆ Differentiation: Pluripotent stem cell –> lymphoid stem cell –> B & T lymphoblasts –> B & T lymphocytes
Maturation of Monocytes
◆Myeloid stem cell line origin, called monocytopoiesis
◆Differentiation: Progenitor cell à monoblast à promonocyte à monocyte
◆2-8% of leukocytes
◆Monocytes remain in blood for 8-16 hours before entering tissues to become macrophages, dendritic cells, other phagocytic cells
B lymphocytes
Originate and mature in bone marrow
●20-30% of lymphocytes
●Humoral response (adaptive immunity), precursor to plasma cells
T lymphocytes
Originate in bone marrow and mature in thymus
●60-80% of lymphocytes
●Cell-mediated response (adaptive immunity), B cell activation
NK cells
Origin is unknown, actions are nonspecific
●
Platelet Production
- Thrombopoiesis
- Progenitor cell megakaryoblast → promegakaryocyte –> megakaryocyte –> platelets
- Megakaryocyte cytoplasm invaginates numerous times that platelets “shed” from to enter circulation from bone marrow
Effects of health, environment and growth factors on normal hematopoiesis (NONE)
Anemia or high altitude can cause oxygen levels to drop due to loss of cells capability to carry oxygen which triggers erythropoiesis
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