blood and hematopiesis Flashcards
Specialized connective tissue consist of cells and extracellular fluid (plasma)
blood
- Plasma gives support and nutrients to the cells present in our blood.
Functions of Blood
○ Transport of oxygen (in different
tissues/ cells of the body) and CO2 (transport back to the lungs).
○ Transport of nutrients and hormones to different parts of the body - to sustain the needs of a person.
○ Removal of metabolic waste.
○ Regulates body temperature and maintenance of acid-base balance - to maintain the body temperature of 37°C.
○ Defense against infection.
■ Example: WBC phagocytize foreign substances.
what are the major cells of the blood
- Erythrocytes aka RBC
- Leukocytes aka WBC
- Thrombocytes aka Platelets
composition of whole blood
PLASMA (55%)
water (92%)
proteins (7%)
- albumin (58%)
-globulins (37%)
- fibrinogen (4%)
other solutes (1%)
BUFFY COAT (< 1% of whole blood)
platelets (150-400 thousands)
leukocytes (4.5-11 thousands)
- neutrophils 50-70%
- lymphocytes 20-40%
- monocytes 2-8%
- eosinophils 1-4%
- bsophils 0.5-1%
RBC (44%)
4.2-6.2 million per cubic mm
ratio of the whole blood of RBC to the volume of blood.
hematocrit
*it is measured by comparing the RBC vol to the plasma volume
What happens to blood after centrifugation?
can see the composition of blood, separating into layers based on density.
What type of tube is used for blood centrifugation?
anticoagulated or non-coagulated tubes
The fluid portion of blood when it is outside the circulatory system and has no anticoagulant.
serum
The fluid portion of blood when an anticoagulant is present.
plasma
A thin, gray-white layer between plasma and RBCs, containing WBCs and platelets.
buffy coat
composition of plasma
- Plasma proteins
- Nutrients
- Respiratory gases
- Nitrogenous waste products
- Hormones
- Electrolytes
what are the Major plasma proteins
Albumin
Globulins (a- and ß-globulins)
Immunoglobulins (antibodies or y-globulins)
Fibrinogen
Complement proteins
Most abundant plasma protein which maintains the osmotic pressure of blood
Albumin
Includes transferrin and other
transport factors such as fibronectin, prothrombin, other coagulation factors, lipoproteins and other proteins entering blood from tissues.
Globulins (a- and ß-globulins)
transport factors such as
- fibronectin
- prothrombin
- other coagulation factors
- lipoproteins
- other proteins
Antibodies used to fight off infection and for defense mechanisms.
Immunoglobulins (antibodies or y-globulins)
- secreted by plasma cells and they are the mature B cells
Important information of fibrin clot in the hemostasis. (clot formation)
Fibrinogen
Involved in the defense system which is important during inflammation and destruction of microorganisms.
Complement proteins
Normal pH of the plasma
pH 7.4
Hematopoiesis in greek
haima - blood
poiesis - making
= blood making
A continuous regulated process of blood cell production.
Hematopoiesis
Includes:
cell renewal
proliferation
differentiation and maturation of cells
what are the phases of hematopoiesis
- Mesoblastic (Yolk Sac) Phase
- Development of primitive (old) erythroblast from mesodermal cells.
○ Origin from the mesodermal cells in the fetus.
[first phase, happening early in the embryo.
Where it happens: In the yolk sac (a temporary structure in the embryo).
What happens: Primitive (early or basic) red blood cells are formed from special cells called mesodermal cells.
These early red cells are not like adult ones—they’re the first version, just to get things started.] - Hepatic Phase
- Occurs during second trimester, liver is the major site of cell production with minor help from spleen.
- Beginning of definitive hematopoiesis.
[beginning of “definitive” hematopoiesis—which means the production of real, functional blood cells like in adults.] - Medullary (Myeloid) Phase
- Start at 5th month of fetal development and remain the primary site of hematopoiesis.
● Production occurs at the developing bone marrow cavity.
○ The development of the blood
cells (hematopoiesis) at the bone marrow cavity of the developing fetus.
○ Site of hematopoiesis for young.
[The bone marrow takes over as the main site of blood cell production, and this continues for life.
Blood cells of all types (RBCs, WBCs, and platelets) are now made in the developing bone marrow cavity.]
What is the main site of blood cell production in the second trimester?
liver, with minor help from the spleen
What are the three blood cell lineages?
Erythroid lineage → Produces RBCs.
Myeloid lineage → Produces WBCs & platelets.
Lymphoid lineage → Produces early lymphocytes .
When does the bone marrow become the main blood cell factory?
during the Medullary (Myeloid) Phase, starting in the 5th month of fetal development.
✔ Blood cell development (hematopoiesis) shifts to the bone marrow.
✔ The bone marrow becomes the primary site of hematopoiesis for life.
blood cells are produced in the Medullary Phase:
-Red Blood Cells (RBCs)
-White Blood Cells (WBCs)
-Platelets
Where does blood cell production occur during the Medullary Phase?
In the developing bone marrow cavity of the fetus.
Pluripotent stem cells in the bone marrow that give rise to all blood cells.
Hematopoietic Stem Cells (HSCs)
- originate from the pluripotent hematopoietic stem cells
- origin of ALL our blood cells
[pluripotent stem cells, which means: → They have the potential to become any type of blood cell.]
What are the two major progenitor lineages from progenitor cells?
Lymphoid Stem Cells
- responsible for the lymphoid line
→ Produces lymphocytes (B cells, T cells, NK cells)
- migrate from BM to other lymphoid organs (thrums, lymph node spleen) for cell proliferation and differentiation
Myeloid Stem Cells
- responsible for the myeloid line
→ Produces granulocytes, monocytes, RBCs, and megakaryocytes
Where do Lymphoid Stem Cells migrate for cell proliferation and differentiation (maturation)
migrate from bone marrow to lymphoid organs like
- thymus
- lymph nodes
- spleen
role of Megakaryocytes
they are large cells in the bone marrow that produce platelets = which help in blood clotting.
What are progenitor cells for blood cells called
Colony-Forming Units (CFUs)
- produce precursor cells (blasts) - basically the start of lineage,
- which later mature into functional blood cells. (they gradually assume the morphological characteristics of the mature functional cell type that they will become.)
What are the four major progenitor cell lineages?
- Erythroid lineage
→ Produces RBCs (Erythropoiesis). - Thrombocytic lineage
→ Produces platelets (Thrombocytopoiesis). - Granulocyte-monocyte lineage → Produces granulocytes & monocytes (Granulopoiesis & Monocytopoiesis).
- Lymphoid lineage
→ Produces lymphocytes & NK cells (Lymphopoiesis)
What is the precursor cell of RBCs
Erythroblast, which matures into an erythrocyte (RBC).
how do stem cells and progenitor cells look under a microscope?
they both resembles large lymphocytes
cannot be easily distinguished
Hematopoietic Growth Factors is also called
Colony-stimulating factors (CSF)/ Cytokines
Glycoproteins that stimulate proliferation of progenitor and precursor cells and promote cell differentiation and maturation within specific lineages.
Hematopoietic Growth Factors (Colony-Stimulating Factors - CSFs)
[- special proteins that help make new blood cells
- send signals to immature cells in the bone marrow, telling them to grow and become different types of blood cells]
what are the types of Hematopoietic Growth Factors:
■ interleukins (ILs)
■ lymphokine
■ monokines
■ interferons
■ chemokines
■ colony stimulating
factors (CSFs)
what are the major hemopoietic cytokines
transes, table 13-1
Supplies semifluid matrix which is responsible for stem cell proliferation, differentiation and provides supporting tissue.
Hematopoietic Microenvironment (Niche)
○ Hematopoiesis depends on the niche. If there is no niche, no one will supply to our cells.
What are the main stromal cells in the bone marrow?
Endothelial cells
- regulate flow of particle entering and leaving the hematopoietic spaces
Adipocytes
- secrete steroids to influence
erythropoiesis and maintain
bone integrity
- regulate volume of bone marrow
Macrophages
- phagocytosis and secretion of
cytokines
Osteoblasts
- bone-forming cells
Osteoclasts - bone-resorbing cells [Break down (resorb) bone]
Reticular cells
- reticular fibers for support
what is the role of the extracellular matrix in the bone marrow?
contains:
proteoglycans
fibronectin
collagen
laminin
hemonectin
thrombospondin
where is the bone marrow found
Medullary canals of long bones (e.g., femur, humerus)
Small cavities of cancellous (spongy) bone (e.g., vertebrae, ribs, sternum, pelvis)
briefly explain the 2 types of bone marrow
- Red bone marrow
○ Abundant in blood and hematopoietic cells = hence the color red.
○ Site where old and defective RBCs are phagocytized by macrophages. - Yellow bone marrow
○ Abundant in adipocytes.
How do we classify the two types of bone marrow?
Based on gross examination
- look at it macroscopically using the eyes
Why is red bone marrow red?
It is abundant in blood and hematopoietic cells.
briefly explain the color of bone marrow in newborns
mostly red bone marrow.
as they mature, it changes to yellow bone marrow.
however, in cases of bleeding or hypoxia, yellow reverts to red marrow to compensate for the need of blood cells.
it is the site of the hematopoiesis and has the most hematopoietic cells.
red bone marrow
What happens to old and defective RBCs in red bone marrow?
phagocytized by macrophages
process of erythrocyte maturation
Erythropoiesis
A growth factor produced by kidney cells that stimulates RBC production.
erythropoietin (EPO)
- produced in the kidneys
- it stimulates the mRNA for protein component of hemoglobin
briefly explain the Stages of Maturation of Erythrocyte
1) Proerythroblast
- the progenitor cell.
- large cell with loose, lacy chromatin, nucleoli and basophilic cytoplasm.
- the basophilia is caused by the large number of free polysomes synthesizing hemoglobin
*if it matures, the degree of basophilia will lessen.
2) Basophilic erythroblast
- slightly smaller with cytoplasmic
basophilia and a more condensed nucleus.
3) Polychromatophilic erythroblast
-reduced cell volume, polysomes and hemoglobin fill cytoplasm.
-reducing regions of both basophilia and acidophilia in the cell.
● can see that some part are somewhat pinkish = acidic violet-ish/ blue-ish = due to basophilia
● however, it slowly turned pinkish when stained
4) Orthochromatophilic erythroblast
- aka normoblast.
- are more dense cells, nuclear volume and more acidic cytoplasm.
- mejo pinkish daw
5) Erythrocytes
- small, anucleated (no nucleus) biconcave cell.
Orthochromatophilic erythroblast also callled
normoblast
Why is the cytoplasm of a proerythroblast basophilic?
Due to the large number of free polysomes synthesizing hemoglobin.
- as it matures, degree of basophilia lessens
A young RBC that still contains some polyribosomes
reticulocyte
- no nucleus
- can be seen when stained with blue cresyl blue
what is the shape and function of erythrocytes
Biconcave disk
– this shape helps in efficient gas transport
- carries oxygen throughout the body.
life span of Erythrocytes
120 days
what are the important proteins needed in erythrocytes
- Hemoglobin
○ Responsible for carrying oxygen throughout different parts of the body. - Band 3
○ Iron transport - Glycophorin A
○ Carries antigenic determinants of blood groups.
○ Example: blood type A and the antigens in the RBC is A antigen and it is responsible for the glycophorin A. - Spectrin
- Ankyrin
*Spectrin and Ankyrin stabilizes the membrane, maintains the cell shape and provides the cell’s
elasticity - requiring the passage to the capillaries.
○ Capillaries has small spaces to pass through the RBC. It needs the shape to be deformed then after passage, it should return to its original shape.
what are the integral membrane proteins of the RBC cells membrane
Band 3 and Glycophorin A
- Integral membrane proteins - maintain the integrity of the RBC (deformation and elasticity).
what is the shape of the deformed RBCs
sickle-shaped red blood cells
- can block blood flow
true or false:
immature RBCs have a nucleus
true - but they lose their nucleus as they mature into erythrocytes.
it is involved in defense against
microorganisms and other foreign agents and in tissue responses to injury.
Leukocytes
what are the 2 major types of leukocytes
Granulocytes:
Neutrophils, Basophils, Eosinophils
Agranulocytes:
Monocytes and Lymphocytes.
[refer to the transes for the
- specific granules
- differential count
- life span
- major functions]
shape of the eosinophils
bilobed or sometimes called headphone-shaped.
Process of granulocyte maturation.
Granulopoiesis
what are the changes during granulopoiesis
○ Synthesis of azurophilic granules
- contains lysosomal hydrolase
- stain with basic dyes
- similar in all types of granulocytes
○ Synthesis of specific granules
- differentiate the three types of granulocyte
● Basophil
● Neutrophil
● Eosinophil
What is the most immature precursor of granulocytes?
Myeloblast
◆ Finely dispersed chromatin
◆ Faint nucleoli
What is the next stage after a myeloblast?
Promyelocyte
- basophilic cytoplasm with azurophilic granules containing lysosomal enzymes and myeloperoxidase
- has different types that
activates different genes that codes for the 3 types of granulocytes
In which stage do granulocytes start showing specific characteristics?
Myelocyte stage
- the visible 3 differences of the 3 lineages of granulocyte.
◆ Basophilic myelocyte - has coarse granules.
◆ Eosinophilic myelocyte - has pinkish and violet- ish.
◆ Neutrophilic myelocyte – has fine, pale granules
What happens in the metamyelocyte stage?
increase in specific granules occupying the cytoplasm.
an intermediate phases where nucleus elongates but it is not polymorphic.
band cell
Segmented nucleus with a polymorphic shape.
matured granulocyte
briefly explain the 4 compartments of neutrophils
- Granulopoietic compartment
- found in the bone marrow - Storage compartment
- found in the red bone marrow
- acts as a buffer system which can release large no. of neutrophils when needed.
■ in bacterial infection, when it needs neutrophils, it will travel
to the site of infection to where the bacteria is and thus release the contents of the neutrophils. - Circulating compartment
- neutrophils are seen in the blood
■ In the circulatory system as they are circulating in the blood. - Marginating compartment
○ neutrophils that temporarily accumulate at the surface of endothelium of the veins.
○ neutrophils migrate to various tissues via diapedesis
what is the indicator of the neutrophil separation
The part na naka pinch, that is the indicator of its separation.
[pinched part between the lobes = nuclear constriction/ chromatin bridge]
[This segmentation indicates the maturity of the neutrophil.
A mature neutrophil typically has 3-5 lobes connected by thin strands.
More lobes = older neutrophil (hypersegmentation may indicate a disorder like vitamin B12 deficiency).]
wht is the color of eosinophil
usually orange-pinkish compared to neutrophil and basophil
process of monocyte maturation
Monocytopoiesis
monocyte > promonocyte > monocyte > macrophage
➔ Monoblast:
large cells identical to monocytes.
➔ Promonocyte:
◆ Basophilic cytoplasm
◆ Large, slightly indented nucleus
◆ Chromatin
◆ Evident nucleoli
➔ Monocyte:
◆ RER
◆ Golgi bodies producing
azurophilic granules
◆ Found in circulation
➔ Macrophage:
◆ Monocytes that migrate in
different tissues
what is the shape of the nucleus in monocyte
kidney-shaped nucleus
it is the process of lymphocyte maturation
Lymphocytopoiesis
○ progenitor cells originate in bone marrow
○ maturation and differentiation occurs in peripheral lymphoid organs (thymus and spleen etc.)
○ The products of lymphocytopoiesis:
B lymphocyte and T lymphocyte has cell surface proteins (CD markers/ Cluster of differentiation marker)
it is the process of platelet differentiation
Thrombocytopoiesis
true or false:
platelets are fragments of megakaryocytes
true
- they are not cells unlike RBC and WBC
it is the most mature cells that originate from the megakaryoblast.
megakaryocytes
- found in the bone marroe n sometimes in the interstital tissue of the skin
A hormone that regulates platelet production.
thrombopoietin (TPO)
- produced in kidney cells
- stimulates thrombocytosis
Megakaryoblast vs megakaryocyte
A. Megakaryoblast
- precursor cell which has a basophilic cytoplasm, large ovoid, kidney-shaped-nucleus, often w several nucleoli
B. Will then mature to megakaryocyte
-a giant cell with polypoid large nucleus, coarse chromatin, numerous mitochondria, RER and golgi bodies responsible for the production in specific granules.
it is the branching process of the
megakaryocyte.
proplatelets
[which help form platelets]
- structures form the framework of proplatelets: Actin filaments and microtubules.
- also has a loop of microtubules that helps form platelet = gives proplatelets their teardrop-shaped enlargement at the end of proplatelets to form platelets
What gives proplatelets their teardrop-shaped enlargement?
A loop of microtubules that helps form platelets.
why do platelets need to be stained under a microscope?
to identify them properly, as they are small and colorless without staining.
what are the 2 partes of the platelets
◆ Hyalomere:
part of cytoplasm without the granules, the halo lang.
◆ Granulomere:
presence of granules.
platelets aggregating around the
polymorphonuclear neutrophils and other cells which causes pseudoneutropenia.
Platelet satellitism
- adhere to the neutrophils
- machine could not count the platelets as it is based on the size of the cells that is ez to detect
Where should mature (segmented) blood cells be found?
in the blood vessels
What does it mean if blasts (precursor cells) appear in circulation?
means that the bone marrow is releasing blast even though they are not mature
- indicates leukemia or severe bleeding, as the bone marrow releases immature cells to compensate for blood loss
changes during erythropoiesis
cell and nuclear volume decreases
chromatin density intensifies until nucleus appears pyknotic and extruded from cell
decrease no. of polyribosomes thus decrease basophilia
increase in hemoglobin amt.
disappearance of other cell organelle
what stage cells is found is usually found in the circulation
segmented (mature) cells
What does it indicates when the presence of blasts or precursor cells in the bloodstream
it indicates an underlying problem
the BM is releasing immature cells b4 they r fully mature
- commonly observes in patients w leukemia or severe bleeding as the bone marrow attempts to compensate for blood loss
specific name of the macrophages, depending on where it settles
In the liver →
In the lungs →
In the brain →
In the bone →
Kupffer Cells → In the liver
Alveolar Macrophages → In the lungs
Microglia → In the brain
Osteoclasts → In the bone
in the process of thrombopoiesis, where can megakaryocytes be found
bone marrow
interstitial tissue of the spleen
in the process of lymphocytopoiesis, where does the progenitor cells originate
in the bone marrow
in the process of lymphocytopoiesis, where does the maturation and differentiation occur
in the peripheral lymphoid organs
the principal physiological regulator of platelet production
thrombopoietin, TPO
- produced by kidney cells
A disease when platelets are aggregating around the polymorphonuclear neutrophil and other blood cells
pseudothrombocytopenia
how do you avoid platelet satellitism
By practice, if the specimen you collected is from EDTA, you may use the citrated or blue-top tube to avoid platelet satellitism
