Blood Flashcards
Composition of blood
- Plasma: water, electrolytes, plasma proteins, hormones, fats, aa, vitamins, carbs, lipoproteins, etc
- RBCs (40-45%)
- WBCs + Platelets
If you add an anticoagulant and centrifuge, then it sediments into layers due to different densities: RBC > WBC > plasma
Cytology of RBC
- No nucleus or most organelles
- Hemoglobin –> acidophilic
- Biconcave disk maximizes SA for respiratory exchange
- Flexible, elastic membrane to allow extravasation
- Spectrin & actin for cytoskeleton
Life span & function of RBCs
- Life span: ~120 days; surface area decreases w age–> rigid sphere
-
Fxn:
- oxygen & CO2 transport by providing an environment for hemoglobin (globin + iron-containing heme)
- has some enzymes for glycolytic & hexose monophosphate biochemical pathway
Blood O2 content in each type of bv: venous, lung, arterial, capillaries
The amount of O2 is highest in arteries and lung capillaries
Less in capillaries, where exchange occurs between blood & tissue
Least in venous
Hereditary spherocytosis
Defect in spectrin or ankyrin binding of spectrin –> round/convex, brittle RBC cell membrane
–>Gets trapped in splenic microcirculation and destroyed in large numbers (hemolysis).
Anemia
Iron deficiency from impaired RBC formation or excessive RBC destruction -> Inadequate hemoglobin –> weakness, pallor, breathlessness.
Hypochromic, microcytic RBCs.
Hemolytic anemia
RBCs are structurally abnormal and thus liable to damage, so they’re removed prematurely and in excess by the spleen
Seen in hereditary spherocytosis and sickle cell anemia (point mutation in hemoglobin gene)
Reticulocytes
Less mature RBCs released from bone marrow up to 2 days ago
Cytology of reticulocytes
Contains residual RNA –> blueish color
Red-blue in Wright stain, Blue in methylene blue
Makes up 1-2% of red blood cells
Neutrophils/neutrophilic granulocytes cytology
-
Prominent, lobed nucleus
- Less mature neutrophils have a band-shaped or horse-shoe nucleu
- Most numerous WBC in an adult
- Azurophilic (primary) & Specific (secondary) granules
- Glycogen, filaments, microtubules
Azurophilic (primary) granules
vs
Specific (secondary) granules
-
Azurophilic granules:
- Large, electron-dense
- Contain antibacterial substances for innate immunity.
- Ex) Myeloperoxidase (can be stained), elastase, cathepsins, defensins
-
Specific granules
- Myeloperoxidase-negative
- Proteolytic enzymes secreted into extracellular environment. Ex) lactoferrin
- Variable size, shape, density
___ granules appear first during neutrophil formation, but as the cell matures, their number falls and __ granules becomes twice as numerous.
Primary first
Secondary next
Frq of neutrophils
lives ~1-4 days, but half-life in blood is only 6-8 hours. It moves into the tissues in response to infection to tissue damage (myocardial infarct)
Functions of neutrophils
Active phagocytes against microorganisms, esp bacteria
Bone marrow will release more neutrophils in resonse to stimuli such as
bacterial infection, tissue necrosis, etc.
Neutrophil phagocytosis
- Chemotaxis attracts the neutrophil to devitalized tissue, bacteria, foreign bodies, complement components
- Blood borne antibody (IgG) to bind to surface antigen on bacteria
- Complement C3b binds Fc end of the antibody to activate complements, or neutrophil binds it (opsonization) for phagocytosis.
- Takes up particles in a phagosome
- Phagosome fuses with neutrophil granules (esp primary)
- Bacteria’s killing is enhances by hydrogen peroxide & superoxide
- Forms a residual body of degraded material
Eosinophils
- Most have bilobed nucleus (N)
-
Ovoid-shaped granules (G)
- Stain bright orange in a Romanowsky stain
- In an EM slide, you can see a dense filamentous core of major basic protein (MBP) called crystalloids (C)
- Contains lysosomal enzymes
Eosinophils circulate for ~8hrs.
What is eosinophils’ function?
Increased in parasitic infections (attacked by major basic protein); allergic reactions to stimuli like pollen; some drug drug reactions
Phagocytoses antigen-antibody complexes and inactivates mediators of inflammation like Leukotrienes.
Basophils cytology
- Nucleus has 2-3 lobes, but often hard to see because of
-
Large, dark purple specific granules containing
- heparin (anticoagulant)
- histamine (vasodilator)
- leukotriene, serotonin, eosinophil chemotactic factor
The least numerous WBC in peripheral blood is
Basophils
Difference between basophils and mast cells
Mast cells are in the bone marrow and tissue
Basophils are in peripheral blood
Basophil function
Hypersensitivity reaction:
- Bind IgE antibody
- When exposed to the corresponding antigen, it will release vasoactive substances
Largest cell in peripheral blood
Monocyte
Monocytes are from bone marrow promonocytes; they spend ~1wk in blood and migrate into tissue where they become ___ or ___. They are the largest cell in the peripheral blood.
Tissue macrophages or histiocytes
Appearance of monocytes
- Large nucleus, usually in an eccentric position
- Pale cytoplasm with fine granules
- Microvilli on cell membrane
Function of monocytes
- Enters the tissue to differentiate into macrophages or tissue histiocytes
- Helps with antigen interaction of immunocompetent cells
Lymphocytes
Single, deeply-stained, spherical nucleus that takes up most of the cell; thin rim of lightly basophilic cytoplasm.
Includes T cells, B cells, and NK cells.
T cells
- Processed by the thymus and participate in cell-mediated immunity (e.g. graft rejection)
- Cytotoxic T cells elaborate cytotoxic agents, making lymphokines.
- Memory T cells survive for yrs/decades
B-cells
- Have immunoglobulin on their cell membrane to aid in humoral or antibody-mediated immunity
- Divide & differentiate into plasma cells in tissue
- Some are memory cells
Plasma cells
derived from B-cells; have an eccenrically placed nucleus
Produces antibodies (immunoglobulins)
NK cells
lack the surface antigens of T and B cells, so they don’t rquire prior stimulation to attack virus-infected or tumor cells
What are the mononuclear WBCs/agranulocytes?
Monocytes & lymphocytes
Neutrophilia (increased circulating neutrophils) indicates ___
Eosinophilia indicates ____
Lymphocytosis indicates ____
Neutrophilia -> bacterial infection
Eosinophilia -> parasitic infections, some allergies
Lymphocytosis -> viral infections
Neutropenia/agranulocytosis (reduced # of circulating neutrophils) can be caused by
bone marrow damage, such as in a tumor or in chemotherapy
diseases (e.g. autoimmune ones, splenomegalies)
Lymphopenia (reduced # of lymphocytes) are associated with some rare inherited diseases, infections, and autoimmune diseases.
E.g. lupus, typhoid, brucellosis
Leukemias
Maligant proliferation of white cell precursors in bone marrow
–> vast # of WBCs that spill over into the blood
chronic vs acute leukemias
Chronic leukemias: well-differentiated proliferating cells; slow progression; bone marrow still produces some normal elements
Acute leukemias: proliferating cells are primitive precursor (blast cells); rapid progression; failure of bone marrow
Platelets are derived from
Bone marrow megakaryotcytes
When platelets become activated, the microtubular system…
Squeezes the granules to the center, releasing the contents, and triggering the coagulation system.
Function of platelets
Hemostasis (stop bleeding) by aggregating and releasing contents of alpha & dense granules –> coagulation cascade involves plasma factors to form a blood clot.
Steps of hemostatsis
- Platelet’s membrane glycoproteins adhere to von Willebrand factor on exposed collagen on damaged blood vessels
- Platelet actin, myosin, and mts cause reversible platelet moulding and adhesion along a broad surface
- Releases granule contents through the canalicular system and synthesize thromboxane
- Thromboxone, ADP, Ca2+ mediate adhesion of other platelets
- Platelet phospholipids (w/ Ca2+) activate blood clotting cascade -> fibrin formation
Thrombocytopenia
Severe reduction in the # of plate lets –> spontaneous bleeding looks like a bruises/patches (ecchymoses)
Thrombocytosis
Excessive circulating platelets due to a burst of bone marrow hyperactivity after acute blood loss.
Name each
A- lymphocyte
B- monocyte
C- neutrophil
D-eosinophil
E- basophil
Unlike plasma, serum lacks
fibrinogen, which is formed in clot formation.
You get serum by centrifuging blood as is, without anticoagulant.
Name these
Neutrohil, eosinophil, basophil
Name these
monocyte, lymphocyte
Whats the disease?
Hypochromic (pale) and microcytic (small) RBCs, central pallor –> less hemoglobin than normal –> iron deficiency –> anemia
Hereditary elliptocytosis
autosomal dominant ; self-association of spectrin subunits, defective binding of spectrin to ankyrin, protein 4.1 defects
-> RBCs are oval
Anemia, jaundice, splenomegaly, and hemolytic anemia are common clinical features of what two diseases?
spherocytosis and elliptocytosis
In sickle cell anemia, glutamic acid is replaced by ____ .
Valine.
-> Hb S causes chronic hemolytic anemia & obstruction of postcapillary venules.
Difference between agranulocytes and granulocytes
Both have primary granules, but only granulocytes have specific/secondary granules
A granulocytes are __nuclear.
mononuclear.
Hypersegmented (too many lobes) neutrophils indicates
Megaloblastic anemia, resulting from vitamin B12 deficiency
