Exam 1 Flashcards
Plasma components
Proteins (albumin, globulins)
Electrolytes (cations/anions)
Nutrients (glucose, fatty acids, triglycerides, amino acids)
Metabolic ‘by-products’ (urea, creatinine, bilirubin)
Signaling molecules (hormones, cytokines, growth factors)
Serum components
Clotted plasma
Clotting factors not present in serum
Used up to coagulate blood (ex: fibrinogen)
Erythrocytes
Red blood cells
Primary function: deliver oxygen
Most abundant
Enucleated in mammals
Platelets
Blood coagulation
Second most abundant
Enucleated granules (mammals)
Smaller than RBCs, round/elliptical, clear cytoplasm
Thrombocytes
Nucleated platelets (non-mammalian)
Similar functions to platelets
Clear to slightly blue cytoplasm, may contain 1-3 small reddish granules in some species
Leukocytes
White blood cells
Protection from exogenous (ex: infectious) and endogenous (ex: cancer) harmful agents
Least abundant
Erythrocyte shapes across species
Normal - biconcave discs
Dog - more typical appearance, largest
Cat - little central pallor, smaller
Goat - tiny, make leukocytes look large
Camelids - elliptical
Deer - “sick shape” when exposed to air (artifact)
Non-mammalians - nucleated
Granulocytes or PMNs (polymorphonuclear)
Neutrophils
Eosinophils
Basophils
(segmented nuclei)
Mononuclear cells
Lymphocytes
Monocytes
How blood clots/coagulates
Upon removal from vessels
Platelets, coagulation proteins (thrombin), & calcium ions
2 ways to inhibit clotting process
Substances that bind calcium (EDTA, sodium citrate for coagulation testing, several citrate containing solutions for transfusions)
Occasionally by inhibition of clotting proteins (heparin) - frequently used to collect blood from very small animals for hematologic and plasma chemistry analysis (provides accurate values for most chemical analyses)
Hematocrit tubes
Anti-coagulated blood centrifuged
Separates into 3 distinct layers:
Plasma, buffy coat (white - platelets, leukocytes), erythrocytes (dark red)
Neutrophils
Most common leukocyte in most species
Larger than RBCs
Clear to slightly granular cytoplasm and lobed nuclei with condensed chromatin
Heterophils
Non-mammalians and some mammals
Function identically to neutrophils, differ by having visible granules on stained smears
Lymphocytes
Second most common leukocyte in most species
Slightly larger than RBCs
Usually have scant light blue cytoplasm and round nuclei which often have heavy matches of nuclear condensation
Monocytes
Third most common leukocyte in most species
Largest and most variable type of leukocyte
Usually abundant cytoplasm that is light blue to grey and foamy to vacuolated
Nuclei vary markedly in shape (amoeboid)
Nuclei may have fissures, indentures, or blebs
Become macrophages upon migration to tissues
Eosinophils
Usually found on blood smears, may be rare
Small, red/orange cytoplasmic granules
Size and shape varies b/w species
Cats have small needle shaped granules
Horses have large, round, intensely stained granules
Segmented nuclei
Basophils
Least numerous in most species
Generally many dark purple granules
Species variation in granule #s and staining
Segmented nuclei
Calcium binding/chelating anticoagulants
EDTA (ethylene diamine tetra acetic acid) - used most often for CBC/hematological purposes
Citrate - used most often for coagulation studies, transfusion purposes
Anti-thrombin anticoagulants
Heparin inhibits coagulation by activating antithrombin, which inhibits the action of thrombin
Occasionally used for hematology and blood chemistry analyses
Useful for small animals because plasma can be analyzed biochemically after hematological analysis has been completed
Hematocrit (HCT)
Similar to PCV in percentage of blood occupied by RBCs
Determined by calculations based on average RBC size (MCV) and count
Packed cell volume (PCV)
Determined by centrifugation of hematocrit tubes and visual measurement
Mean cell (corpuscular) volume (MCV)
Average volume of RBCs
Useful in determining general cause of anemia
Mean cell (corpuscular) hemoglobin (MCH)
Average weight of hemoglobin in RBCs
Not commonly used to interpret data, may be used to detect iron deficiency at early stage
Red cell distribution width (RDW)
Can only be determined by more advanced automated instruments
Provides estimate of variation of RBC size (degree of anisocytosis)
Useful for determining erythropoietic responsiveness of bone marrow to anemia
Coefficient of variation of the MCV
Reticulocyte count
Supravital stain - new methylene blue
Useful for determining responsiveness of bone marrow to anemia (regenerative if increased)
Blood cell lifespans
Neutrophils ~10 hours
Platelets ~10 days (6-10 in circulation)
RBCs ~100 days (correlated with size in mammals)
Some lymphocytes may live for many years
Hematopoiesis in “stress”
Demand for blood cells exceeds production
Bone marrow extends down long bones and yellow marrow becomes red marrow
Sites of fetal hematopoiesis reactivate (spleen, liver, lymph nodes, kidney - extramedullary hematopoiesis)
Circulating stem cells find ‘niche’ in fetal sites
Mammalian hematopoiesis
Occurs outside of blood vessels
Cells cross endothelial lining into vessels when ready (tightly regulated)
Avian hematopoiesis
Granulopoiesis extravascular
Erythropoiesis/thrombopoiesis inside sinuses
No megakaryocytes
Key hematopoietic growth factors
SCF (KIT-ligand)
IL-7, IL-3, IL-5
GM-CSF, G-CSF, M-CSF
Erythropoietin (EPO), thrombopoietin (TPO)
In which disease would you expect to see anemia due to decreased erythropoietin production?
a. renal failure
b. liver failure
c. immune mediated hemolytic anemia
d. fungal infection
Renal failure
Decreased EPO production, decreased erythropoiesis
Bone marrow precursor cell development
Cell size and nucleus size decrease (except in megakaryocytic lineage)
N:C ratio decreases
Nucleoli disappear
Chromatin condenses
Basophilia of cytoplasm decreases as RNA decreases
Specific cytoplasmic contents accumulate (hemoglobin, granules)
Erythropoiesis morphology (erythrocyte precursors)
Rubriblast - prorubricyte - basophilic rubricyte - polychromatic rubricyte - metarubricyte - polychromic erythrocyte/reticulocyte - erythrocyte
Erythroblastic island
Macrophage (nurse cell) surrounded by erythroid precursors
Provide certain cues and growth factors
Iron from macrophage used for hemoglobin
Helps remove dead nuclei
Erythropoiesis features
4-5 mitoses in 5 days (3-6 days)
1 rubriblast = 16-32 RBCs
Hypoxia is stimulus - synthesis of erythropoietin by kidney (liver is secondary source in some species)
Erythropoietin effects
Proliferation of erythroid progenitor cells
Erythroid cell maturation
Hemoglobin synthesis
Early release of reticulocytes
Which of the following cells has the highest hemoglobin concentration?
a. rubriblast
b. basophilic rubricyte
c. metarubricyte
d. erythrocyte
Erythrocyte
Most differentiated - more accumulation
Granulopoiesis morphology (neutrophil precursors)
Myeloblast - progranulocyte - myelocyte - metamyelocyte - band neutrophil - mature neutrophil
Granulopoiesis kinetics
Large # of neutrophils often needed in short time
Storage pool necessary
Small animals - large pool, large animals - small pool
Multiple factors stimulate production (IL-3, GM-CSF, G-CSF)
Most factors produced by cells of immune system
G-CSF (granulocyte colony stimulating factor)
Acts on progenitors, mitotic precursors
Increase # of neutrophils produced
Shortens production and maturation
Neutrophils ready sooner
Increases release of neutrophils from bone marrow
Enhanced tissue emigration and functional capabilities
Used therapeutically
IL-5
Stimulates eosinophil production
Monocytopoiesis
CFU-GM (shared progenitor of neutrophils and monocytes)
Cell lines diverge after CFU-GM
CFU-GM - monoblasts - promonocytes - monocytes
No storage pool for monocytes in BM
Platelet precursors
Different in that they get larger as nucleated precursors mature in marrow
Megakaryoblast - promegakaryocyte - megakaryocyte - break up into platelets
Transfer of platelets from marrow to blood
Megakaryocytes send long pseudopodia into blood
Cytoplasm of pseudopod fragments into platelets
Megakaryocytes shed platelets directly into blood
Platelet production control
Constitutive production of TPO in liver (and kidney)
Platelets bind TPO (inactive)
Increased platelets decrease TPO in blood, vice versa
Thrombocytopenia = more free TPO, increased megakaryopoiesis
Thrombocytosis = less free TPO, decreased megakaryopoiesis
Storage pool in spleen (not BM)
Glucocorticoids induce the release of storage pool neutrophils into circulation. In which animal species would you expect to see higher neutrophilia in response to glucocorticoid stimulation?
Small animal species (dogs/cats) because they have large neutrophil storage pools
