white blood cells Flashcards
which cells exist in the mitotic pool? What about the maturation and storage pool? What is the important difference between these?
-mitotic pool in the bone marrow consists of myeloblasts, promyelocytes and myelocytes
>these cells divide
-maturation and storage pool consists of metamyelocytes, band and segmented neutrophils
>These cells are no longer able to divide
once segmented neutrophils are released into the blood, how long are they there for? Then what?
6-10 hours
-then move into tissues to help with inflammation/infection or apoptose
what are the two pools of neutrophils in circulation? How do these compare in size?
-circulating neutrophil pool, CNP
-marginating neutrophil pool, MNP
> pools of similar size except in cats, who have a larger MNP
what is the avian and reptilian equivalent to the neutrophil?
heterophil
what is the function of neutrophils, and how do they achieve this?
-protect predominantly against bacterial pathogens
>to a lesser degree against fungal, protozoal, parasitic or viral organisms
-Leave the blood stream by diapedesis, where they move through the endothelium of small capillaries, and phagocytose organisms
- chemotaxis controlled by complement system, coagulation of finbrinolytic systems, endotoxins, or chemokines
- recognize pathogens via opsonins
- ingest organism into phagosome
- phagosome fuses with granules
- reactions in phagolysosome kill organism
what cells are often incorrectly identified as WBCs by automated counters?
rubricytes (nucleated RBCs)
what do we call an increase in segmented neutrophils in circulation? What mechanisms can cause this?
-increase in mature circulating neutrophils
1. ephinephrine response - ‘physiologic’
2. stress leukogram
3. acute inflammation
4. chronic inflammation
5. tissue necrosis, neoplasia
what are the characteristics of physiologic neutrophilia? What is the mechanism?
Epinephrine response - ‘physiologic’
• Mild mature neutrophilia, no left shift
• Mild lymphocytosis
-more common in young animals
Mechanism:
Marginating neutrophils move into CNP. Lymphocytes remain in vasculature longer.
what are the characteristics of a stress leukogram? What is the mechanism?
• Mild to moderate mature neutrophilia
• Lymphopenia
• Possibly monocytosis and/or eosinopenia
-influence of cortisol
»Segmented neutrophils, monocytes increased
»Lymphocytes, eosinophils decreased
Mechanism:
Release of bone marrow storage pool of segmented neutrophils, longer circulation time, and decreased margination. Lymphocytes are retained in lymph nodes.
what are the characteristics of neutrophilia due to acute inflammation? what is the mechanism?
• Neutrophilia with moderate to marked left shift
Mechanism:
Depletion of segmented neutrophils and release of band (or younger) neutrophils from bone marrow
what are the characteristics of neutrophilia due to chronic inflammation? what is the mechanism?
• Marked neutrophilia with variable left shift
Mechanism:
Increased production and release of segmented neutrophils from bone marrow
what are the characteristics of neutrophilia due to tissue necrosis or neoplasia? what is the mechanism?
• Mild to marked mature neutrophilia, often with a left shift
Mechanism:
Cytokine-mediated increased production of neutrophils
what species may have only mild changes in neutrophil numbers despite marked inflammation? why?
mature ruminants, due to a smaller reserve of cells
what species produces a greater magnitude of neutrophilia in response to inflammation: dogs and cats vs horses and ruminants?
cats and dogs have neutrophilia of a far greater magnitude: 6-10x, vs 2-3x for horses and cows
in terms of inflammation, what does the degree of neutrophilia correlate with? What about the degree of left shift?
The degree of neutrophilia correlates with the intensity of the inflammatory stimulus, and the degree of left shift with acuteness
how does neutrophilia differ for contained vs draining lesions?
contained lesions hvae no ability for supprative material to leave
-draining have lower neut count, less stimulus for neut production as things can get out
what are leukemoid reactions?
‘similar to leukemia’, very high neutrophil counts
how does neutrophilia after surgical removal of a lesion behave?
-normal to find lots of neutrophils after surgery until down regulation occurs in the marrow; body has a delayed response to lesion removal
what are the two broad ways that neutropenia can occur?
- Tissue demand exceeds bone marrow storage
- Decreased neutrophil production
what do we see when tissue demand for neutrophils exceeds bone marrow storage? When does this occur?
neutropenia
• Occurs with acute suppurative inflammation
• Cattle often develop neutropenia in these circumstances
• Toxic changes and a left shift are common
what is a regenerative left shift?
segmented neutrophils outnumber band and metamyelocyte (or more immature) neutrophils
what is a degenerative left shift?
band and metamyelocyte neutrophils (or more immature) outnumber segmented neutrophils
what do we see when we have neutropenia due to decreased neutrophil production?
insults on dividing cells in the bone marrow: cytotoxic drugs, radiation therapy, estrogen toxicity, and parvovirus infections
- Due to the short life span of neutrophils their numbers are more affected than platelets and red blood cells
-Neutrophil counts below 0.5 x 106 strongly predispose to secondary infections, and thus are life-threatening.
how do most insults to the bone marrow manifest?
first with neutropenia, then with anemia or thrombocytopenia
toxic changes in neutrophils
dhole bodies
cytoplasmic basophilia
cytoplasmic vacuolization
what are dhole bodies
neutrophil toxic change, aggregates of rough ER
what is cytoplasmic basophilia
increased cytoplasmic RNA
what is cytoplasmic vacuolation
autophagocytosis
when do we see neutrophil hyposegmentation?
left shift - tissue demand exceeds bone marrow stores of segmented neutrophils. Usually accompanied by toxic changes.
pelger-huet anomaly - mutation where granulocyte cells do not segment. neutrophils function normally.
>dogs and cats, rare horse.
>may be congenital or acquired
what are the physical characteristics of eosinophils?
• Pink-orange granules in the cytoplasm
• Segmented nuclei (at least 2 segments)
• Long tissue phase in some disease conditions
• Cytoplasmic granules contain compounds particularly toxic to complex parasites (i.e. major basic protein)
what is major basic protein and what is it good for?
component of eosinophil granules, effective against parasites
what is the basic process by which an eosinophil reaches its target site?
-leukotrines and chemokines attract eosinophil to target location
-selectins allow for rolling, integrins for adhesion
-eosinophils migrate into tissue and become active
what are the physical characteristics of basophils? are they common? how long do they spend in tissues?
• Blue-purple granules in the cytoplasm
• Segmented nuclei
• Produced in the bone marrow
• Rare in blood
• Short circulation time, and generally short time in tissues
what are the physical characteristics of mast cells? where are they derived, and where do they mature?
• Deep blue granules as well, but round nucleus, not segmented
• Derived from bone marrow, but
mature in tissues, not in bone marrow
which cells have preformed inflammatory mediators?
• Basophils and mast cells have preformed
inflammatory mediators
what is the lineage of the monocyte and what is its purpose?
monoblast > promonocyte > monocyte
Monocytes give rise to tissue macrophages and to antigen-presenting cells important in the immune response
what is the lifespan of a monocyte?
2-3 days (compared to 5-7 days for most other blood cells)
is there a storage pool for monocytes?
no
when do monocytes increase?
Increase with corticosteroid therapy, fungal
infections, some inflammatory conditions
(esp. chronic)
what types of lymphocytes are there?
-natural killer cells
-CD4+ T-lymphocyte (helper)
-CD8+ T-lymphocyte (cytotoxic/suppressor)
-plasma cell (B-lymphocyte)
function of CD4+ T-lymphocyte
production of cytokines to help B‐cells and cytotoxic lymphocytes
function of CD8+ T‐lymphocytes
killing of virus-infected cells
function of B cells
produce antibody
characteristics of lymphocytes: lifespan, function, residence, how do numbers change?
Long-‐lived and re-‐circulate
Surveillance of body
Inhabit mucosal sites
Can undergo clonal expansion and retraction
what are 6 ways that monocytosis can arise?
- Chronic inflammation (granulomatous or
pyogranulomatous) - Fungal infections
- Immune hemolytic anemia
- Bacterial infections
- Corticosteroid excess
- Recovery from bone marrow suppression
how are macrophages,
dendritic cells,
neutrophils, and
CD4 lymphocytes activated? What are the possible outcomes?
Bacterial phagocytosis or exposure activates macrophages, dendritic cells, neutrophils, and
CD4 lymphocytes. The outcomes can either be augmentation of the inflammatory cascade, or downregulation of the inflammatory response through production of specific cytokines.
what are 4 ways that eosinophilia can arise?
- Allergic reactions
- Parasitic infections
- Pulmonary infiltrates with eosinophils
(eos. bronchopneumopathy) - Hypereosinophilic syndrome:
-‐ leukemia
-‐ Mast cell neoplasia, lymphoma, rare
other neoplasms
how can basophilia arise?
- Parasitic infections
- Eosinophilic inflammation
eg.
Heartworm
Intestinal parasites, in particular Strongyle spp.
in horses
Fleas
Habronemiasis in horses
Mast cell tumors in dogs and cats
what are 5 ways that lymphocytosis can arise? Can acute infections manifest with lymphocytosis?
- Epinephrine-‐mediated
- Recent vaccination
- Chronic infections i.e. ehrlichiosis
- BLV infection in cattle
- Lymphocytic leukemia
**Acute infections with
enlarged lymph nodes rarely
manifest with lymphocytosis.
what are 4 ways lymphopenia can arise?
- Corticosteroid induced
- Acute infections, in particular viral infections
- Loss of lymphocyte-‐rich fluid: chylothorax,
lymphangiectasia - Immunodeficiency
which cell of hematopoietic origin can become neoplastic?
all of them
what does leukemia refer to?
• Leukemia refers to neoplastic cells in circulation, arising from a hematopoietic organ such as bone marrow or spleen
what is the difference between chronic and acute leukemia in broad terms?
• Chronic leukemias are more slowly progressive, and often have a greater accumulation of neoplastic cells
• Acute leukemias typically present as very sick animals that rapidly progress to death
what are 6 characteristics of acute leukemia? ie. what are some things we can look for to diagnose vs chronic?
• Circulating blast cells
• Hyper or hypo-‐cellular BM
• Minimal maturation
• Organomegaly uncommon
• May be dysplastic
• Pancytopenia
what are 6 characteristics of chronic leukemia? ie. what are the ways we can differentiate it from acute?
• Predominant cell type is mature
• Hypercellular BM
• Maturation present
• Organomegaly common
• Relatively normal morphology
• No cytopenias or anemia only
4 things we look for to make a leukemia diagnosis
- Abnormal cells in blood or bone marrow
- Usually myelophthisis (“crowding out”) of normal
cells in the bone marrow – therefore anemia,
neutropenia, and/or thrombocytopenia - Usually require blood smear and bone marrow
examination - Treatment: Depends on the type of leukemia,
but limited options in veterinary medicine
what are the types/subcategories of leukemia?
- lymphoprofliferative
-acute
-chronic
>can immunophenotype as B or T cell origin - Myeloproliferative
-acute
-chronic
>Subtyped based on morphology and markers
* Myeloid (granulocytes)
* Monocytic
* Erythrocytic
*Megakaryocytic/platelets
what is a myelodysplastic syndrome?
one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia.
what are the possible causes and consequences of a myelodysplastic syndrome?
-genetic mutation (or cytopenia) leads to accelleratied proliferation
>cause marrow hypercellularity
-accelerated proliferation leads to improper maturation
>cause dysplasia
=>leads to apoptosis, development of cytopenias
=>cytopenias can make problem worse in feedback loop
what is lymphoma associated leukemia?
cancer arises in lymphoid tissue, not bone marrow
up to half of all dogs with mymphoma have this condition. What is difficult about this?
Lymphoma-‐associated leukemia
-hard to distinguish between this and bone marrow related leukemia
