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110 Cards in this Set

  • Front
  • Back
Where does the blood cells arise in the early embryo (2-8 weeks)?
Yolk sac (mesoderm) produces blood islands
Where does hemopoiesis occur during 2nd trimester - birth?
Mainly in the liver, spleen plays a minor role too
Where does hematopoiesis occur during 3rd trimester - adulthood?
Bone marrow
*Hematopoiesis in post-natals is exclusively in the bone marrow
Structure of the bone marrow:
Reticular fibers
Veins
Arteries
Sinusoids 
Island of cells
Reticular fibers
Veins
Arteries
Sinusoids
Island of cells
(Blood sinusoids appear white)
The two types of bone marrow include?
Red marrow: active hematopoiesis
Yellow marrow: fat in reticular cells, inactive hematopoiesis
Production of blood cells include:
* >10^9 (billion) cells produced daily
All blood cells arise form a single major type of pluripotent stem cell in the bone marrow
* As cells develop, they decrease in size, nuclei condense
* >10^9 (billion) cells produced daily
All blood cells arise form a single major type of pluripotent stem cell in the bone marrow
* As cells develop, they decrease in size, nuclei condense
Stem cells forms 2 major lineages of progenitor cells, which are the...?
Myeloid cell: colony forming units
Lymphoid cell (Lymphocytes): colony forming units

*Both types are multipotential cells
Myeloid cell: colony forming units
Lymphoid cell (Lymphocytes): colony forming units

*Both types are multipotential cells
The myeloid lineage includes:
Precursor cells (blasts) for:
erythropoiesis
thrombopoiesis
granulopoiesis
monocytopoiesis
*All in the Bone Marrow
The lymphoid lineage forms...
Lymphopoietic cells
T Lymphocyte
B Lymphocyte --> Plasma cell
NK lymphocyte
*Partly in the bone marrow & partly in Lymphoid organs
What is the difference between progenitor cells and precursor cells?
Progenitor cells (colony-forming units) are committed to a single cell line with limited self renewal ability
Precursor cells (blasts) are morphologically distinct, No self renewal
What is the regulation for hematopoiesis ?
1. hematopoietic growth factors (colony stimulating factors)
2. interleukins, granulocyte colony stimulating factor, erythropoietin
3. stem cell factor (steel factor) - stromal cells of the bone marrow, stimulates division
4. hematopoietic cells will die unless exposed to grown factors
Erythropoiesis is controlled by?
Cytokines and Erythropoietin (kidney)
takes ~ 3-5 days to complete development
~ 2 x 10^9 erythrocytes per day
Identify this cell
Identify this cell
Proerythroblast (Erythropoiesis)
14-19 um
No hemoglobin
Large nucleus
Basophilic cytoplasm
Basophilic (early) erythroblast (Erythropoiesis)
12-17 um
some Hemoglobin
Condensing nucleus
Polychromatophilic erythroblast (Erythropoiesis)
12-15 um
"muddy" cytoplasm
Orthochromatophilic (late) (Erythropoiesis)
8-12 um
increased hemoglobin
Reticulocyte (Erythropoiesis)
7-8 um
No nucleus
some Ribosomes
(blue with Cresyl Blue stain)
Erythrocyte (Erythropoiesis)
7.5 um
Only Hemoglobin
No Ribosomes
Reticulocytes
What are the 2 arrows pointing to?
What are the arrows pointing to?
Identify this cell
Identify this cell
What does Granulocytopoiesis (granulocyte formation) include and what controls it?
Controlled by cytokines, takes ~11 days
1. Myeloblasts
2. Promyelocyte
3. Myelocyte
4. Metamyelocyte
5. Band
6. Mature form
Controlled by cytokines, takes ~11 days
1. Myeloblasts
2. Promyelocyte
3. Myelocyte
4. Metamyelocyte
5. Band
6. Mature form
What cell is this?
Myeloblasts (Granulocytopoiesis)
Common precursor
12-14um
No Granules
Cytoplasmic blebs
Promyelocyte (Granulocytopoiesis)
16-24um
large Nucleus
Azurophilic granules (not specific)
Myelocyte (Granulocytopoiesis)
10-12 um
condensed rounded nucleus
specific granules
Metamyelocyte (Granulocytopoiesis)
Kidney-shaped nucleus
specific granules
Mature form of granulocytes include:
Neutrophil
Eosinophil
Basophil
Neutrophil
Eosinophil
Basophil
"BEN"
Identify this cell
Identify this cell
A neutrophil with a segmented nucleus
*Neutrophils may be subdivided into segmented neutrophils (or segs) and banded neutrophils (or bands).
Characteristics of Band (stab) granulocytes are:
C-shaped nucleus
specific granules
C-shaped nucleus
specific granules
*Before neutrophilic granulocyte reaches its complete maturation, it passes through an intermediate stage --> Band (Stab) cell
Identify these cells
Identify these cells
What is Thrombopoiesis and what controls it?
= Platelet formation
Controlled by Thrombopoietin
What are some of the important components for thrombopoiesis?
1. Megakaryoblast (25-40 um, endomitosis, polyploid ~32N)
2. Megakaryocyte (40-100 um, large multi-lobed nucleus)
3. Platelet demarcation membranes
4. Proplatelets
What is the function of megakaryocyte?
It is a bone marrow cell responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting
*Platelets are formed from fragments of megakaryocyte cytoplasm
What are platelet demarcation membranes?
They are mature megakaryocytes that have numerous invaginations of plasma membrane ramifying throughout the cytoplasm
This membrane system (D) is a reservoir of membrane used during elongation of the numerous proplatelets which extend from the me...
They are mature megakaryocytes that have numerous invaginations of plasma membrane ramifying throughout the cytoplasm
This membrane system (D) is a reservoir of membrane used during elongation of the numerous proplatelets which extend from the megakaryocyte surface
What are proplatelets?
The elongated branching processes extended from megakaryocyte cytoplasm --> to form platelets
Identify this cell
Identify this cell
Identify this cell
Identify this cell
Process of Monocytopoiesis (Monocyte formation) includes:
1. Monoblasts (large, undifferentiated)
2. Promonocytes (16-18um, kidney-shaped nucleus, azurophilic granules)
3. Monocytes ("sky" blue cytoplasm, kidney-shaped nucleus)
4. Macrophages (when entered the circulation)
Process of Lymphopoiesis (lymphocyte formation) includes:
1. colony forming units (CFU) - lymphocytes (B & T)
2. Lymphoblasts: Large, undifferenciated
3. Prolymphocytes: medium-sized cells, condensing chromatin, No cell surface antigens
How are T-cells (T lymphocytes) made?
When hematopoietic progenitor cells migrate from bone marrow to thymus
How are B-cells made?
When hematopoietic progenitor cells remain in the bone marrow, they differentiate to B-cells migrate to lymph tissues
What is Pancytopenia?
= a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets
*Due to failure of bone marrow to produce blood cells
What are the two approaches used to identify causes of bone marrow failure?
1. Consider causes of peripheral destruction: hypersplenism, sepsis, immune-mediated
2. Perform bone marrow investigation
a. Hypercellular marrow
b. Hypocellular marrow
Hypercellular marrow may indicate:
Peripheral destruction
Hypersplenism
MDS
Marrow infiltration
Hematologic malignancy (Solid tumor; Storage disease; other)
Megaloblastic anemia
Myelofibrosis
Hypocellular marrow may indicate:
Aplastic anemia
Drugs/chemicals
Viruses
Radiation
Fanconi anemia
Idiopathic
What are storage diseases?
Examples?
--> affect bone marrow (and other tissues)
Most common bone marrow storage disease are:
Gaucher's disease
Niiemann-Pick disease
What cause Gaucher's disease?
Due to Deficiency of the enzyme Glucocerebrosidase
(helps body process the fatty substance glucocerebroside)
When does Gaucher's disease occur?
When certain harmful fatty substances accumulate to excessive levels in the liver, spleen, lungs, bone marrow, and brain (less common)
What is Niemann-Pick disease?
Congenital deficiency in lysosomal sphingomyelinase.
Results in
Sphingomyelin, cholesterol and glycolipid accumulation in macrophages in liver, spleen, bone marrow, hepatocytes, and CNS cells
What is Myelodysplastic syndrome?
A group of disorders caused by poorly formed or dysfunctional blood cells
NO CURE!
Can only prolong life when treated with bone marrow transplant
What is Fanconi anemia (FA)? and what is the outcome?
Rare, Inherited blood disorder that leads to bone marrow failure.
FA prevents the bone marrow from making enough new blood cells
FA can cause to make many faulty blood cells
*Result in serious health problems, eg. Leukemia
Multiple myeloma is?
Cancer of plasma cells
(Plasma cells normally make antibodies)
Viruses that suppresses immune system are:
Parovovirus B19
Dengue
Hepatitis viruses
Epstein-Barr virus
Cytomegalovirus
Human Immunodeficiency Virus (HIV)
Pancytopenia can result in which 3 things?
Increased destruction --> Immune destruction sepsis
Sequestration --> Hypersplenism
Decreased production --> Myelodypalsia; Marrow infiltrate; B12 deficiency; Aplastic anemia; Drugs; Viruses; Radiation
Defective RBC formation may result in?
Anemia
Hemorrhage
Deficient erythropoiesis
Accelerated destruction of circulating RBCs
Deficiencies of Fe, Vit. B12, Folic acid
Defective WBC formation may result in?
Inflammation
Allergic rxn
Hypersensitivity rxns
Infections
Leukemia
4 Main types of Leukemia are:
1. Acute lymphoblastic leukemia (ALL) --> mostly children
2. Acute myelogenous leukemia (AML) --> both children and adults
3. Chronic lymphocytic leukemia (CLL) --> mostly adults >55 yo; rare in children
4. Chronic myelogenous leukemia (CML) --> mostly in adults
Defective platelets formation may lead to?
Bleeding problems (increase / decrease)
Thrombocytosis (or thrombocythemia) --> due to high platelet counts in blood
Thrombocytopenia --> decrease of platelets in blood
Identify all the cells.
Identify all the cells.
Blue arrow = Myelocyte
Yellow arrow = Metamyelocyte
Black arrow = Neutrophil
Blood
Specialized connective tissue
o Cells
o Matrix
• Ground substance
• Fibers
Blood CT
Matrix --> Plasma
No fibers (differentiates from other CT)
Bone marrow
All of the several blood cell types originate in the BM
WBC (Lymphocytes and monocytes) --> Move freely back and forth between blood and other connective tissues
Plasma
Aqueous Solution
•7% protein
Albumin --> Maintains osmotic pressure of blood
Gamma globulins -->Immunoglobulins or antibodies
Fibrinogen --> Clotting agent
10% lipoproteins
•Amino acids
•Vitamins
•Hormones
•Inorganic salts
Formed elements
Cells
Platelets
Blood component:
RBC = Erythrocytes = 44%
WBC = Leukocytes and platelets = 1%
Plasma = 55%
Blood smears used
Blood smears used
Leishman
Wrights
Giemsa or May-Grunwald-Giema stains
Modified Romanowski Stain!
Methaline blue and eosin
Red blood cells – erythrocytes
Biconcave discs
Non-nucleated
Acidophilic (Stained reddish with eosin)
Main protein = Hemoglobin + O2 = Oxyhemoglobin
120 day life span
Males has more blood count than females (menstruation)
Carbonic anhydrase (CO2 transportation)
Enzyme of glycolytic and HMP shunt pathways
ABO blood group system
Rh antigens ‑ Rh+ vs Rh‑
Most common blood type
Type O,
A
B
AB
Universal donor
Type O
No antigens = no clumping
Universal recipient
Type AB
No antibodies = no clumping
How does blood typing work?
Whatever type blood a person is, that’s the antigen present on their blood…
- Example, if your blood type is A, you have A antigen on it
- Type B = Type B antigen
- TYPE O has NO ANTIGEN
If someone was Type A blood, they would have A antigen and have B antibodies on their blood
- Type B, as type B antigen, and A antibodies …
- Type AB has NO ANTIBODIES
Rh System
Rh positive = antigen present, no antibodies
Rh negative = no antigen present, antibodies will be produced IF exposure occurs
Erythroblastosis fetalis (also called Rh disease) --> Rh negative mother & Rh positive father have an Rh positive fetus
Rhogam = passive immunity (treatment for Rh disease)
Clinical applications
-Erythrocyte membrane deformation – cytoskeletal organization "Spectrin"
-Anisocytosis (abnormal variation in cell size (macro and microcytosis)
-Poikilocytosis (altered cell shape (sickling, crenation)
Hemoglobin
Composed of globin
4 highly folded polypeptide chains
4 heme groups with iron
Each molecule carry 4 moles of oxygen
Oxyhemoglobin
Reduced hemoglobin when not carrying oxygen
Can carry carbon dioxide
Sickle Cells
-Single point mutation that codes for globin produces HbS hemoglobin with a single amino acid difference at point 6 on the B chains
-Substitution of hydrophobic valine for hydrophilic glutamic acid
-Valine is in sickled gene
White Blood Cells – leukocytes
Granulocytes
Neutrophils
Eosinophils
Basophils
Agranulocytes
Lymphocytes
Monocytes
Types of blood cells from most to least amount.
NEVER LET MONKEY EAT BANANA’s
- Neutrophils ~60% (50-70%)
- Lymphocytes ~30% (20-40%)
- Monocytes ~5% (1-9%)
- Eosinophils ~3% (0-5%)
- Basophils ~0.5% (0-2%)
Granulocytes
-Irregular segmented nuclei
-Specific granules (specific size, staining affinities, ultrastructure)
-Terminal (fully differentiated) cells
Agranulocytes
-Regular nuclei (round or kidney-shaped)
-Non-specific granules
Processes exhibited by Leukocytes
Chemotaxis
Amoeboid movement
Diapedesis
Neutrophils
Eosinophils
Chemotaxis
Chemical attraction which stimulates WBC (esp Neutrophils and monocytes) to sites of infection
Amoeboid movement
WBC motility in which pseudopodia are extended and the rest of the cell pulled forward in “crawling” action
Diapedesis
WBC flatten and move through the vascular wall into the interstitial tissue
Neutrophils
also called neutrophilic granulocytes / polymorphonuclear neutrophilic leukocytes, PMNs, or polys
= most numerous of the leukocytes ~60% of the WBC count
Twice the size of RBC
What are the characteristics of Neutrophils?
Very characteristic nucleus
Divided into 3-5 lobes connected to thin strands of chromatin
Lobes can increase with cell age (up to 7) = hypersegmented cells
Very characteristic nucleus
Divided into 3-5 lobes connected to thin strands of chromatin
Lobes can increase with cell age (up to 7) = hypersegmented cells
The 2 types of granules of Neutrophils are:
1. Primary (A) granules
Contain Lysosomal enzymes
2. Secondary (B) granules
Contain enzymes with strong bactericidal actions
*Granules of neutrophils are weakly stained
Function of the Neutrophils:
•Inflammatory process
•Invades sites of infection in response to cytokines, released by cells invading infection sites
•First to come to invading site
•Receptors in plasma membrane allow them to recognize and phagocytosize and destroy
•Tags with antibodies (or opsonized)
•Cannot replenish their store of granules
•Cell dies once their supply of granules has been exhausted. Dead neutrophils and tissue debris are the major components of pus
•Life span is 1 week
Eosinophils
10-15 um
2 lobes
Short life span (few days)
Granules
10-15 um
2 lobes
Short life span (few days)
Granules
Granules of Eosinophils include:
Specific and non-specific (azurophilic/acidophilic)
a. Specific: large granules (crystalloid-major basic protein, enzymes)
b. Non-specific: lysosomes; hydrolytic enzymes
Specific and non-specific (azurophilic/acidophilic)
a. Specific: large granules (crystalloid-major basic protein, enzymes)
b. Non-specific: lysosomes; hydrolytic enzymes
Function of Eosinophils:
1. Destroy antibody‑antigen complexes and parasitic worms
2. Release major basic protein involved in killing parasites
3. Engulf and destroy antibody‑antigen complexes
Basophils
8-12 um
less than 0.5-1% of leukocytes 
Granulocytes
Have 2 or 3 lobed nucleus
S shaped
Not well defined nucleus
Granules are stained bluish or reddish-biolet
Granules
8-12 um
less than 0.5-1% of leukocytes
Granulocytes
Have 2 or 3 lobed nucleus
S shaped
Not well defined nucleus
Granules are stained bluish or reddish-biolet
Granules
Granules of Basophils include:
Specific
• Large granules (heparin, histamine, leukotriene)
Non-specific (azurophilic)
• Lysosomes, hydrolytic enzymes
Functions of Basophils:
•Heparin and histamine (vasoactive substances)
•Dilate blood vessels, make vessel walls more permeable and prevent blood coagulation
•Facilitate access of other lymphocytes and plasma-bourne substances of importance for the immune response (antibodies) to a site of infection
•Release of the contents of the granules of basophils is receptor-mediated
•Antibodies produced by plasma cells (activated B lymphocytes) bind to Fc Receptors on the plasma membrane of basophils
Mast cells:
1. binding of antigens (to IgE) releases specific granules
2. histamine ‑ vasodilation, smooth muscle contraction, etc.
3. heparin ‑ anticoagulant
Identify cells
Identify cells
Monocytes:
12 ‑ 25 um
Kidney or C shaped nucleus
No specific granules
Pale blue cytoplasm
Life span (few days in circulation/months in tissues)
Granules: non-specific (azurophilic) - lysosomes
12 ‑ 25 um
Kidney or C shaped nucleus
No specific granules
Pale blue cytoplasm
Life span (few days in circulation/months in tissues)
Granules: non-specific (azurophilic) - lysosomes
Functions of Monocytes:
become tissue macrophages after migration
1. avid phagocytes (dead cells, antigens, bacteria)
2. produce cytokines ‑ initiate inflammation, etc.
3. antigen‑presenting cells
4. foreign body giant cells (multinucleated)
Lymphocytes
8-18 um
Lifespan (Months to years)
Round, dense nucleus
No specific granules
Small, blue cytoplasm
Granules: non‑specific (azurophilic) – lysosomes
Immune response
8-18 um
Lifespan (Months to years)
Round, dense nucleus
No specific granules
Small, blue cytoplasm
Granules: non‑specific (azurophilic) – lysosomes
Immune response
Function of Lymphocytes
immune response (B cells, T cells, null cells)
1. B cells become plasma cells ‑ produce antibodies
2. T cells kill viral cells, produce cytokines
3. null cells ‑ stem cells, natural killer cells
Platelets:
2-4 um
No nucleus
Cell fragments from megakaryocyte
Hyalomere (Outer region hardly stains, peripheral tubuler system, increase surface area)
Granulomere (Dense core with granules and few organelles, stains bluish)
Granules
Count: 250,000 ‑ 500,000
Granules of Platelets include:
alpha, delta, lambda (lysosomes)
a. alpha: fibrinogen, platelet derived growth factor, [PDGF]etc.
b. delta: calcium, serotonin, ATP, etc.
c. lambda: lysosomal (hydrolytic) enzymes
Function of Platelets:
-Assist in hemostasis (arrest of bleeding)
-Damaged vessels …walls and platelets secrete substances to mediate the conversion of the plasma protein prothrombin into thrombin.
Thrombin catalyzes the conversion of fibrinogen into fibrin, which polymerizes into fibrils and forms a fibrous net in the arising blood clot
-Platelets captured in the fibrin net contract leading to clot retraction
Intrinsic pathway
-XII gets converted by HK/PK to XIIa
-XI gets converted by Ca2/HK to XIa
-IX gets converted by CA2 to IXa
...
Platelet function:
1. circulating platelets; endothelial damage
2. platelet adhesion
3. platelet aggregation
4. platelet-fibrin plug
5. clot retraction
1. circulating platelets; endothelial damage
2. platelet adhesion
3. platelet aggregation
4. platelet-fibrin plug
5. clot retraction
Some Anomalies:
Inappropriate clotting
Excessive bleeding
Inappropriate clotting due to:
a. thrombus - clot formed in an intact vessel, possibly due to:
roughened vessel walls (atherosclerosis)
slow-moving blood (e.g., in varicose veins) = small quantities of fibrin form & accumulate
b. embolus - 'moving' clot
Excessive bleeding due to:
a. Hemophilia
genetic "defect"
inability to produce certain factor(s)
b. Thrombocytopenia
abnormally low platelet count
most persons have idiopathic thrombocytopenia (= unknown cause)
in others it's an autoimmune disease