Lecture 24: Hematology Flashcards
What kind of tissue is blood?
Connective
How do we determine the components of blood?
First centrifugation, then add anticoagulant, you obtain 3 layers: plasma on top, leukocytes (with platelets top layer) in buffy thin layer, and erythrocytes on bottom
What is the role of the anticoagulant after centrifugation of blood?
W/o anticoagulant: clot (bottom) and serum (top)
What makes up the 3 formed elements of blood?
RBCs, WBCs, and platelets
What is another name for WBCs?
Leukocytes
What does plasma consist of? Provide %s
Water (90%) and solute (10%)
What are the 2 types of WBCs?
Agranulocytes and granulocytes
What is the differential count?
The % of different types of leukocytes in blood
What was used to determine the differential count prior to hospitals having automated hematology blood analysis?
Romanovsky-type stain
What is the hematocrit? What is the normal range?
The packed cell volume of blood: 40-45% is the normal range
What are the 3 types of solutes in plasma? What does each include?
- Proteins 2. Small organics: lipids, carbs (mainly glucose), AAs, wastes (urea, creatinine, bilirubin) 3. Inorganics: mainly electrolytes
What are the 3 plasma protein types? Include %s.
- Albumin (60%) 2. Globulins (35%) 3. Fibrinogen (4%)
What is the role of albumin?
Contributes to osmotic pressure and binds loosely to other molecules
What are the 2 types of globulins?
- Immunoglobulins 2. Transport globulins
What is another name for immunoglobulins?
Antibodies
What is the role of fibrinogen?
To facilitate the formation of blood clots
What is another name for RBCs?
Erythrocytes
Do RBCs have a nucleus? What does this mean for their lifespan?
Not in humans Short lifespan of 120 days
What is the shape of RBCs? What does this allow?
Drumstick: allows them to squeeze through capillaries
Where are RBCs produced?
Bone marrow
How long does it take to produce RBCs?
7-8 days
Can RBCs repair their DNA or proteins? Why/Why not?
NOPE because they do not have a nucleus
How are RBCs removed from the body?
Hemolysis
Where does hemolysis occur? 4 spots
- Mainly in ECF of spleen 2. Liver 3. Bone marrow 4. Intravascular compartment (by macrophages): 10% of hemolysis
What are the 3 components of the RBCs’ membrane?
- Glycophorin 2. Anion transporter channel (band 3) 3. Ankyrin
Describe glycophorin.
RBC transmembrane protein on outer surface
What is the role of the anion transporter channel (band 3)?
RBC membrane channel that allows bicarbonate to cross the membrane in exchange for Cl- allowing the release of CO2 in the lungs
What is the role of ankyrin?
RBC membrane protein that anchors band 3 (at the spectrin dimer) to the subcellular cytoskeleton within the cytoplasm
What are the 3 sugar moeities for the ABO blood groups?
- A: N-acetylgalatosamine (GalNac) glycosidically bonded to O antigen (at galactose)
- B: α-D-galactose glycosidically bonded to O antigen (at galactose)
- O: Lipid-Glucose-Galactose-N-acetylglucosamine-Galactose-Fusoce (LGGNGF)
What is anemia? What is it caused by (4 causes)?
Low hemoglobin concentration in circulatory system Causes: 1. Hemorrhage 2. Insufficient RBC production (kidney damage = lower EPO) 3. RBCs with insufficient Hb (Iron deficiency) 4. Accelerated RBC destruction
What hormone stimulates the production of RBCs? Where is it produced?
Erythropoietin (epo) produced by kidneys
In what type of people do we see low levels of RBCs? Why?
Old people because their diseased kidneys cannot secrete epo
What disease causes accelerated RBC destruction?
SCD
In what type of people is iron deficiency common? Treatment?
Pregnant women because the fetus is using all of the iron
Treatment: iron supplement
What are the 3 types of granulocytes?
- Neutrophils 2. Eosinophils 3. Basophils
What is another name for neutrophils?
Polymorphonuclear leukocytes
What is the differential count of neutrophils?
60-70%
How can one identify neutrophils?
They have a lobulated nucleus when they are first formed and as they age there are more lobulations
How many neutrophil lobulations mean they are at the end of their lifespan?
5-6
What are the 2 types of neutrophil granules?
- Non-specific granules = AZUROPHILIC 2. Specific granules
Describe the non-specific granules of neutrophils. What do they contain?
Primary lysosomes that contain myeloperoxidase and acid hydrolases
What color do non-specific neutrophil granules stain?
Purple
What does it mean for a cellular object to be azurophilic?
Readily stainable with a Romanowsky stain
Describe the specific granules of neutrophils. What do they contain?
Contain proteases and lysosymes
What color do specific neutrophil granules stain?
Pink
Are neutrophilic specific granules visible under a microscope?
Yes, but at the resolution limit
What is a Barr body?
Distinguishing feature of neutrophils which is an injected piece of nucleus: inactive X chromosome
What does the presence of a Barr body on a neutrophil indicate?
The sample is from a female
What is the main function of neutrophils?
Phagocytose and kill bacteria
What is diapedesis?
The way neutrophils and eosinophils exit the vasculature by squeezing through spaces between endothelial cells
What is chemotaxis?
The way neutrophils and eosinophils can migrate in response to chemotactic factors to the site of infection
What are the 2 mechanisms neutrophils use to kill bacteria? Describe each.
- Oxygen-dependent: O2 is converted to superoxide radicals who are converted to hydrogen peroxide, which can be converted to hypochlorous acid (bleach) in the presence of myeloperoxidase (MPO) ⇒ BASICALLY BLEACHING BACTERIA
- Oxygen-independent: lysosomal degradation
What can the production of superoxide radicals by neutrophils and macrophages (inflammatory cells) cause? How?
Cancer through inflammation: they leak out of the cell and damage cells in the infected area, when cells repair there may be a mismatch repair leading to genetic mutation and if enough of them, cancer
What is another name for superoxide radicals?
Reactive oxygen species
What can reduce the presence of ROS and therefore cancer?
Anti-oxidants and NSAIDS (this is used as a chronic treatment for risk of colorectal cancer)
What is the differential count of eosinophils?
2-4%
How can one identify eosinophils?
Prominent colored STRIPED granules in nucleus and not as lobulated as neutrophils
What is the internum? What is it composed of (3 elements)?
The stripe of the eosinophil granule Composed of: 1. Major basic protein that attacks parasites 2. Eosinophil cationic protein 3. Neurotoxin
What is the externum? What does it contain?
The part of the eosinophil granule that surrounds the internum and contains peroxidase and hydrolytic enzymes
What is the major function of eosinophils?
To attack parasites and limit inflammation
How do eosinophils downregulate inflammations?
By inactivating leukotrienes and histamine
What is the role of leukotrienes?
They stimulate smooth muscle contraction in the lungs
How does chemotaxis happen for eosinophils?
They are recruited by eosinophil chemotactic factor secreted by basophils
What is the differential count of basophils?
0.5%
How can one identify basophils?
They have a lobulated nucleus but lobules are hard to see because of darkly stained basophilic granules
What do the granules of basophils contain? 4 elements.
- Heparin (anticoagulant) 2. Proteases 3. Histamine 4. Eosinophil chemotactic factor
What do histamines cause? What can this result in?
Vascular permeability which can result in localized edema making it easier for molecules to make it to the site of infection
What is the role of basophils? Explain how this works.
Major role in inflammation: they have IgE molecules on their surface that acts as a receptor and binds antigens/allergens (2 IgE for 1 antigen) which leads to a transduction cascade with calcium mobilization to release basophilic factors that facilitate the inflammatory response (usually after exposure to allergen):
- Granule mediators
- Lipid mediators
- Cytokines
What are the 3 types of agranulocytes?
- Lymphocytes 2. Monocytes 3. Mastocytes
What is the differential count of lymphocytes?
28%
How can one identify lymphocytes?
Nucleus fills almost the entire cytoplasm and is round or oval and no granules
What is the function of lymphocytes?
They mediate both humoral and cellular immunity (B and T cells)
How will the number of lymphocytes be affected by infection?
Increase
How will the number of lymphocytes be affected by an autoimmune disease?
Decrease
What is the differential count of monocytes?
5%
How can one identify monocytes?
By process of elimination: no granules, nucleus not as big as lymphocytes, and has weird shapes for its nucleus
What is the function of macrophages? How does this work?
Help stimulate the immune response as part of the antigen presenting cell family: phagocytose an antigen, break it down with lysosymes, and present on MHC-II complex on surface to helped T-cells which stimulate B cells to secrete antibodies
What do the monocytes differentiate into once they are out of the vasculature?
Macrophages
What cells have an MHC-II complex?
Antigen Presenting Cells (APCs)
What cells have an MHC-I complex?
All
What are platelets?
Cell fragments
What are the 2 parts of a platelet? What does each consist of?
- Hyalomere: peripheral microtubules and microfilaments around the outside
- Granulomere: central portion with granules and lysosomes
What are the 3 types of granules contained in the granulomere of a platelet? What does each secrete and for what?
- Alpha granules: secrete PDGF which promotes endothelial cell mitosis at vascular injury site 2. Delta granules = dense core granules: secrete serotonin to promote vasoconstriction 3. Lambda granules = lysosomes
What happens when there is a vascular injury?
- Blood vessel constricts to reduce blood loss (thanks to serotonin) 2. Collagen fibers exposed and sticky 3. Platelets stick to fibers (subendothelial collagen) to form a plug 4. Clotting cascade where fibrinogen is converted to fibrin 5. Fibrin binds to platelets to form a definitive hemostatic plug
What causes hemophilia A?
Genetic disease: absence of factor VIII (Von Willebran’s factor), a clotting cascade protein
What does blood transport?
- O2 and nutrients 2. Wastes 3. Hormones 4. Heat 5. Cells
What is it called when your hematocrit is too high?
Polycythermia
What is it called when your hematocrit is too low?
Anemia
What color do eosinophils stain?
Orange
What color do basophils stain?
Blue
How to prepare a romanovsky type stain?
Put a drop on one slide and then pull a slide back on it and then in the other direction: causes the feathered edge (density is thicker at the base of it and end of it is one single layer)
What does a lower differential count for any of the leukocytes indicate?
Possible leukemya
What do transport globulins bind?

- Small ions
- Hormones
- Others

Do all organisms have RBCs without nuclei?
Nope, chichens do for example
What does the integrity of an RBC during its lifespan depend on? 3 things
- Cell membrane
- Hb
- Metabolic enzymes
What is SCD caused by?
Point mutation in Hb changing Glu to Val
What are the different layers the O2 has to pass through from the lungs to the RBC? 7 of them
- Fluid and surfactant layer
- Alveolar epithelium
- Epithelial basement membrane
- Interstitial space
- Capillary basement membrane
- Capillary endothelium
- RBC plasma membrane
Where are sickled RBCs hemolysed?
Spleen
Do all neutrophils have a Barr body? Always visible?
Yes in women, but sometimes hiding under lobulated nuclei
What are 2 examples of parasites? What attacks it?
Helminthic worms or shistosome larva
Eosinophils
Which element of the internum of eosinophils attacks parasites?
Major basic protein
Other than basophils, what other cells secrete eosinophil chemotactic factors?
Mast cells
What is hemostasis?
The stopping of a flow of blood.
What system are monocytes part of?
The mononuclear phagocyte system
What is the earliest stage at which specific granulocyte types can be distinguished from one another?
Myelocyte