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45% cells
red, blood, platelets
Hematopoeisis
ALL blood cells, so red and white blood cells but NOT platelets since they are not cells.
fetal liver ——> RED bone marrow
only accounts for 1% of bone marrow but the stem cells can regenerate in the bone marrow after an injury.
Hematopoeisis also occurs in liver and spleen which is extramedullary usually when the bone marrow fails.
Pluripotent stem cells
are stimulated by cytokines, interleukins, and hormone
Myeloid
G - granulocytes (eosinophils, basophils, neutrophils)
E - Erythrocytes
M - megakaryocyte
M - macrophage
Macrophages
go to the spleen to mature
Megakaryocytes
stay in the bone marrow and the platelets are released into the bloodstream
Both T and B can be found
mostly in the lymph node but also in the peripheral blood
RBC
begins as a nucleated cell within the bone marrow
As the RBC matures
The cellular diameter decreases
•The nucleus becomes denser and smaller, and
•The nucleus is finally released from the cell (extruded) to
become an anuclear biconcave disk.
Erythroprotein
stimulates the pluripotent cell to become a committed erythroblast
glycoprotein in response to low levels of oxygen hypoxia
● Accelerates the rate of mRNA and protein
(hemoglobin) synthesis,
Decreases the time for the maturation of
orthochromatic normoblasts,
Stimulates the premature release of
immature RBCs, reticulocytes and orthochromatic normoblasts,
from the bone marrow,
Increases the rate of extrusion of an RBC
nucleus (enucleation) in the later stage of RBC maturation.
Orthochromic normoblast
nucleated RBC
Polychromatic erythrocyte
reticulocyte
anucleated
Pronormoblast
Percent in bone marrow: 1%
● Hours in bone marrow: 12 hours
● Overall size: 12 to 20 micrometers
● Nucleus to cytoplasm ratio: 8:1
● Nucleus: Round to oval shape with 1 or 2 nucleoli;
chromatin has fine clumps
● Cytoplasm: Intensely blue
Basophilic normoblast
Percent in bone marrow: 1% to 4%
● Hours in bone marrow: 20 hours
● Overall size: 10 to 15 micrometers
● Nucleus to cytoplasm ratio: 10:1
● Nucleus: Some chromatin clumping, no (or 1) nucleoli
● Cytoplasm: deeper, richer blue than blast
Polychromatic normoblast
Percent in bone marrow: 10% to 20%
● Hours in bone marrow: 30 hours
● Overall size: 10 to 12 micrometers
● Nucleus to cytoplasm ratio: 4:1
● Nucleus: No nucleoli, clumpy chromatin
Orthochromic normoblast
Percent in bone marrow: 5% to 10%
● Hours in bone marrow: 48 hours
● Overall size: 8 to 10 micrometers
● Nucleus to cytoplasm ratio: 1 to 2
● Nucleus: Nucleus is almost or completely pyknotic;
incapable of DNA synthesis
● Cytoplasm: Pink-orange; slightly bluish hue
Polychromatic erythrocyte
After a few days in the bone marrow as
reticulocytes, the RBCs squeeze through an opening
in the endothelial lining of the marrow cavity and enter
the peripheral circulatory system.
● The number of reticulocytes (percentage) in the
peripheral blood is an indication of the degree of RBC
production by the bone marrow.
Reticulocyte
Become fully mature within 1 or 2 days in the circulating blood and all RNA disappears
24-48 hours in bone marrow.
bluish hue
Heme consists of two things
Fe2+, protophyrin ring
Porphyrin ring
is excreted from the body as bilirubin.
Carbaminohemoglobin
Hb returning to the lungs with CO2 from tissues
As erythrocytes age
The concentration of cellular hemoglobin increases.
● Enzyme activity, particularly glycolysis, diminishes.
● When these changes reach a critical point, the RBC
is no longer able to move through the
microcirculation
Worn out RBCs
are removed by the mononuclear phagocytic system (spleen)
Extravascular catabolism
aged or abnormal RBCs are removed by splenic or
hepatic macrophages
● Normal physiologic function
Intravascular catabolism
Destruction of RBCs within the blood vessels
● Normal in small amounts
● Abnormal ex. complement destruction, disseminated
intravascular coagulation, thrombotic
thrombocytopenic purpura, heart prosthetics
Increased hemoglobin present in intravascular catabolism
damage to kidney
Increased hemoglobin catabolism (intra- and
extravascular
can be seen with increased levels of birubilin (jaundice)
Sickle cell anemia
Hemolytic anemia
Mean Corpuscular Hemoglobin
indicates average weight of hemoglobin per cell (pg)
MCV range
80 - 100 fL
MCH range
27.5 - 33.2
MCHC
33.4-35.5
Normochromic-normocytic anemias
peripheral blood film
the cells are produced are normal but the NUMBER IS REDUCED
Blood LOSS
Macrocytic anemia
hypersegmented mature neutrophils in the peripheral blood
Hypochromic microcytic anemia
MOST common
increased requirements during lactation, pregnancy, infancy
has globin deficiencies
Can also result from disorders in globin synthesis, porphyrin synthesis, and heme synthesis
Hypochromic-microcytic anemia - globin
Thalassemias, a group of inherited disorders of Hb
synthesis.
● Disorder in the rate of globin synthesis
● Must differentiate between 𝛂 or 𝛃 Thalassemia
● Alpha Thalassemia (1 - 4 gene deletion)
● Beta Thalassemia (1 or both gene mutatio
thalassemia minor = INCREASED RBC
Hemolytic anemia
RDW is greatly increased in hemolytic anemia because of anisocytosis = and poikilocytosis.
Classified as acquired or congenital
Anisocytosis
Difference in size
poikilocytosis.
difference in shape of membrane
Most severe form of G6PD deficiency is
acute hemolytic anemia, exposed to a drug or have an infection
Band features
Overall size: 10 to 16 micrometers
● Nucleus to cytoplasm ratio: 1:1
● Nuclear characteristics: Elongated, curved
● Cytoplasmic characteristics: Specific blue-pink
granules
Band neutrophils
The band neutrophil is a younger form of the mature
neutrophil.
● Band neutrophils resemble segmented cells except for
the shape of the nucleus. An increase in their numbers
is significant.
Characteristics of neutrophils
contain several digestive enzymes that are able to destroy many types of bacteria.
• The cells are capable of random locomotion and
can be directed to an area of infection by the
process of chemotaxis.
• They move back and forth between the general
blood circulation and the walls of the blood
vessels, where they accumulate.
Eosinophil
Overall size: 10 to 16 micrometers
● Nucleus to cytoplasm ratio: 1:1
● Nuclear characteristics: Distinct lobes (usually bilobed, occasional three lobes)
● Cytoplasmic characteristics: Orange (acidophilic) granules
Slightly larger than neutrophils,
active in allergic reactions and
certain parasitic infections, especially those
involving parasitic invasion of the tissue
Basophil
Overall size: 10 to 16 micrometers
● Nucleus to cytoplasm ratio: 1:1
● Nuclear characteristics: Distinct lobes, but can vary in shape (lobular to slightly indented)
● Cytoplasmic characteristics: Blue-black granules
irregularly shaped nucleus
cytoplasm is usually colorless
Monocyte
Mature monocyte
• Overall size: 12 to 18 micrometers
• Nucleus to cytoplasm ratio: 2:1 to 1:1
Monocytes remain in the peripheral blood for hours to days after leaving the bone marrow.
● They are motile, phagocytic cells, but they do not die after they engage in phagocytic activity (neutrophils do die)
indented nucleus
auzurophilic granules
Lymphocyte
Overall size
• Small: 6 to 9 micrometers
• Large: 17 to 20 micrometers
• Nucleus to cytoplasm ratio
• Small: 4:1 to 3:1
• Large: 2:1
• Nuclear characteristics: Round or oval
• Cytoplasm characteristics: Light blue; few
azurophilic granules may be presen
B lymphocyte
generation of mature, end stage, non-motile cells
Auer rods
Slender, rod-shaped bodies found in the
cytoplasm of myeloblasts or monoblasts
Leukamoid reaction
Leukamoid reaction: primary cells affected are neutrophils, a shift to the left so more immature cells. NON-malignant, NO blasts
Barr bodies
Small knob attached to neutrophil nucleus;
thought to be an inactivated X chromosome
May-Heggelin anomaly
Blue inclusion bodies seen in neutrophils
Chediak Higashi Syndrome
Syndrome is inherited, rare, autosomal recessive, close relatives, decrease in phagocytosis
Acute myelocytic (acute non-lymphoblastic
leukemia, ANLL) leukemia (AML
Blast # greater than or equal to 20%
Chronic myeloproliferative disorders, including
chronic myelogenous leukemia (CML
Blast # less than 20%. Chronic can become acute
Acute lymphoblastic leukemia
Typically in younger populations
Malignant changes - changes other than leukemia
Plasma cell dyscrasias such as multiple
myeloma
• Hodgkin disease
• Non-Hodgkin malignant lymphomas
• Unusual tumors
Hemostasis
balances numerous interdependent coagulation factors that prevent bleeding
thrombus plug
Primary hemostasis
FOrmation of a platelet plug
Secondary hemostasis
blood clot
thrombus
stop the bleeding
Unbalanced hemostatic system
Thrombosis
platelet-derived growth factor.
The endothelium of blood vessels is repaired and maintaine
Normal Platelet Count
150-450×10^9 /L
Thrombocytopenia causes
Heparin therapy, alcoholic liver disease, after the use of extracorporeal circulation
Echhysmosis
Excessive bruising
Petechiae
Small hemmoraghic spots
Quantitative platelet disorders are caused by
drug-induced dysfunction most commonly due to aspirin
ingestion,
● uremia due to renal dysfunction,
● liver disease,
● acquired or inherited von Willebrand disease or
● paraneoplastic platelet dysfunction associated with plasma cell
dyscrasias, e.g., multiple myeloma
Factor 1
Fibrinogen
Factor 2
Prothormbin
Factor 3
Tissue thromboplastin
Factor 4
Ionized calcium
Factor 5
Labile Factor
Factor 6
Factor Va
Factor 7
Proconvertin
Factor 8
Antihemophilic factor
Factor 8:vWF
Von Willebrand Factor
Factor 8
Stuart Power Factor
Factor 11
Plasma Thromboplastin anticedant
Factor 12
Hageman Factor
Factor 13
Fibrin stabilizing factor
Vascular system and the coagulation cascade are in
constant states
Platelets form receptors that bind to…
fibrin
What will happen if the clot were not allowed to breakdown?
blockage, stroke, restricted blood flow
Hemostatic mechanism
the entire process by which bleeding from an injured blood vessel is controlled and finally stopped
aPTT range
25-38
PT INR
0.8-1.2
Hemophilia A
VIII Deficiency
Hemophilia B
IX deficiency
Hemophilia A range
Normal adult: 55–170 U/dl
• Normal infant: 93–302 U/d