Hematology Exam 2

leukocytes

responsible for recognition, response, and removal of foreign material and damaged or dead cells/tissue from the body; MAJOR participants in both the inflammatory and immune response mechanisms

neutrophils, eosinophils, basophils, (small) lymphocytes, and monocytes

What are the 5 types of leukocytes?

pools

various collections of leukocytes throughout the body; leukocytes are not freely circulating in the blood and instead are found switching back and forth between these areas

proliferation pool

leukocyte cells that are being formed in the bone marrow that will be available upon maturation are found here

storage pool

mature leukocyte cells stored mainly in the spleen and bone marrow are found in this type of area

proliferation pool and storage pool

What are two pools that consist of leukocyte cells not yet released into circulation?

circulating pool and marginal pool

What are the two pools within the vasculature where leukocyte cells are found?

circulating pool

free moving leukocyte cells (this is where we draw our blood samples)

marginal pool

leukocyte cells that are stuck to or rolling along the walls of small vessels and not freely circulating; surprisingly, this pool contains 50-75% of the cells

tissue pool

made up of leukocytes that have left the blood vessels to enter various areas of the body; where most of the WBCs function

diapedesis

when leukocytes migrate out of the vessels through the vessel wall into the tissues

blood vessels

function essentially as a means of transport between pools

disease conditions or hormonal influences

What can cause cells to shift between pools?

very rapid, within minutes to hours (corticosteroids or epinephrine)

How long is the response time of leukocytes from marginal and storage pools?

much slower than marginal and storage pools

How fast is the response time of new leukocytes from the proliferation pool?

neutrophil

What is the most predominant leukocyte in the peripheral blood of dogs, cats, horses, and humans?

common myeloid progenitor

What progenitor cell produces leukocytes?

myeloblast, promyelocyte, myelocyte, metamyelocyte, band, then -phil

What is the maturation order of a granulocyte?

neutrophils

continuously produced; present in circulation 6-7 hours prior to migrating out and into tissues and body activities; may live 2-3 days in tissues but if a disease is present, may only survive a few hours; bone marrow maintains a 5 day supply of these

phagocytosis (engulfing small particles/organisms and breaking down by enzymes) and inflammation

What are the major functions of neutrophils?

polymorphonuclear (PMNs) or Segmented (segs)

What are some names used to describe the nucleus of a neutrophil?

- most easily recognized feature is the segmented nucleus with its 3-5 lobes

- nuclear chromatin is coarse, clumped, and dark staining

- cytoplasm varies blue to pink, but most common is clear

- very small dust-like granules usually too small to be visible on a microscope (neutral)

What are some descriptions of normal neutrophil morphology?

band cell

a juvenile neutrophil; nucleus has a ribbon-like or band appearance and has roughly parallel sides and diameter stays > 50%

Barr Body

a club-like appendage of the nucleus; seen in neutrophils collected from a female dog; appears to be an inactivated X chromosome

heterophils

avian and reptile neutrophils; granules are larger, oblong, and stain red to pink

left shift

increased number of immature neutrophils present; causes an increased demand for neutrophils results in more immature forms released from the bone marrow

right shift

increased # of hyper-segmented neutrophils present (body tells them to stay); causes neutrophils staying in circulation longer due to increased cortisol/glucocorticoids and artifacts in old blood samples;

when there is a rapid loss and increased demand for neutrophils, as in infections and tissue damage, the increased release rate from the bone marrow will often contain a larger percentage of immature forms; increase of band numbers and creates toxic neutrophils

What occurs in a left shift of neutrophil numbers?

regenerative left shift

when the number of immature forms that are present remain equal to or less than the mature, segmented neutrophils; this indicates a proper bone marrow response

non-regenerative left shift

the total leukocyte and neutrophil counts may be normal, but usually begin falling and the number of immature neutrophils exceeds the mature forms; both the marginal and storage pools have been depleted and the bone marrow can't keep up with the demand (poor prognosis in most species)

hyper-segmented neutrophil

any neutrophil with more than 5 nuclear segments and represents increased aging of the cell; presence of excessive numbers of these cells in circulation is called a right shift

when an excessive number of hyper-segmented neutrophils are seen in circulation; may be seen when the neutrophil has remained in the circulation longer than normal due to presence of corticosteroid from stress or a treatment regimen; may also see as an artifact in blood samples that have been stored too long

When does a right shift occur in neutrophil numbers? Why may it be seen?

toxic neutrophils

seen during infections and inflammation; production is increased causing the maturation time to shorten; some immature features remain

- cytoplasmic basophilia

- vacuoles

- Dohle bodies

- small basophilic granules

What are some toxic changes seen in the cytoplasm?

cytoplasmic basophilia

streaky, diffuse, irregular blue appearance of the cytoplasm in a blood smear

Dohle bodies

light bluish-staining inclusions in the cytoplasm of the neutrophil; remnants of endoplasmic reticulum (of immature neutrophils); indicates increased neutrophil production

cytoplasmic granules

seen w/ increased neutrophil production where maturation is rushed; when fewer mitotic divisions, the promyelocyte granules are not diluted or removed; more common in horses and ruminants

vacuoles

occur with lysosome degranulation possibly associated with phagocytosis; can also see with an old blood sample

- Ehrilichiia

- Histoplasma

- Distemper Inclusion Bodies

- Hepatozoon

What are some infections agents that can be seen through abnormal neutrophil morphology?

Chediak-Higashi Syndrome

hereditary disorder where neutrophils have a small number of lightly eosinophilic, moderately sized granules; neutrophils have decreased function, so see recurrent infections

Pelger-Huet anomaly

hereditary disorder found in many breeds of dogs and an occasional cat; is the failure of the nucleus in neutrophils and eosinophils to segment; will appear as band cells

Birman Cat Neutrophil Granulation Anomaly

hereditary disorders where neutrophils have normal function but their granules just stain differently

neutrophilia

increased number of circulating neutrophils; rapid increases in neutrophil numbers due to shifting of cells from the marginal and storage pools into the circulating pool

- infectious organisms pyogenic (pus-forming) bacteria

- inflammation - tissue necrosis (trauma)

- neoplasia

- various intoxications

- presence of corticosteroids or epinephrine, whether administered or endogenous due to excitement or stress

What are some causes of neutrophilia?

neutrophilic leukocytosis

leukemia response marked neutrophilia so high it indicates chronic inflammatory response

leukocytosis

all WBCs are increased

neutropenia

decrease in neutrophils in circulation; generally due to a rapid movement of the cells out into the tissue pool or a decrease in cells available from proliferation and storage pools; can be temporary if neutrophils responding to infections (cattle)

- bone marrow suppression from viral or chemical agents

- overwhelming bacterial infections

- sequestration of cells in capillary beds in endotoxic, septic, or anaphylactic shock

What are some causes of neutropenia?

phagocytes

What are a group of cells that specialize in finding and engulfing pathogens called?

granulocytes, macrophages, and dendritic cells

What are the three types of phagocytes?

apoptosis

A natural killer T cell injects cytotoxin into an infected cell, which then perforates the cell membrane. This is called?

cell-mediated

What type of immune response occurs when Helper T's are activated due to the antigen presentation process?

memory; plasma

During humoral immunity, B cells start to produce clones, some of which turn into ________ cells or ________ cells.

lymphocytes

What type of cells have specialized receptors that only match to one specific antigen?

lymphocytes

second most numerous WBC type in the blood of dogs, cats, horses, and humans; most numerous in ruminants

lymphatic system

composed of lymph vessels, lymph nodes, thymus, spleen, GALT, and certain blood vessels

gut associated lymphoid tissues

GALT; includes appendix, parts of SI and LI, certain blood vessels

- transport and store lymphocyte cells within the body

- filter out dead cells and invading organisms (bacteria)

- where lymphocytes mature

What are the hematological functions of the lymphocyte system?

lymphopoiesis

process where lymphocytes originate in the bone marrow; maturation time in bone marrow of 2 - 5 days

lymphoblast, prolymphocyte, lymphocyte --> leaves bone marrow as NK cells and small lymphocytes, further maturation and multiplication occurs after leaving the marrow

What are the steps of lymphopoiesis?

mature lymphocyte

when a lymphocyte has the ability to distinguish "self" from "non-self" antigens

1. leave bone marrow as a generic, immature, small lymphocyte

2. become T-cells in the thymus

3. mature in lymphoid tissue (thymus, lymph nodes and spleen)

4. when activated multiply and diverge into: helper Ts, regulatory Ts, cytotoxic Ts, and memory Ts

What are the steps of lymphopoiesis that T cells go through?

1. leave bone marrow already a B-cell

2. mature in lymphoid tissue (spleen and lymph nodes)

3. when activated multiply and diverge into: plasma cells and memory cells

What are the steps of lymphopoiesis that B cells go through?

70% T-lymphocytes; 30% B-lymphocytes; circulation 8-12 hours and survive days to years

What is the ratio of T-lymphocytes to B-lymphocytes in the blood? How long does it take them to circulate throughout the body and how long do lymphocytes live?

lymphocyte receptors

each lymphocyte equipped with one of these to match to one specific antigen (except NK lymphocytes); many different types of these

- round(ish) nucleus with smooth dense chromatin

- scant, pale blue cytoplasm

What is the normal morphology of lymphocytes?

reactive lymphocytes

seen when lymphocytes are antigenically stimulated; caused by infections, vaccinations and neoplasia

- larger cells

- more cytoplasm, often deeper blue

- nucleus tends to be less dense and more lacey

How do reactive lymphocytes appear on blood smears?

atypical lymphocytes

caused when lymphocytes are bent/pulled out of shape when smear is made, especially when the blood is allowed to sit; seen with both normal and reactive lymphocytes; no need to report to DVM

lymphocytosis

increased number of lymphocytes circulating in blood

- physiological causes: very young animals, fear, excitement, epinephrine, increased muscle activity

- antigenic stimulation: viruses, blood parasites, post-immunization

- lymphosarcoma/lymphocytic leukemias

When are some times we see lymphocytosis?

antigenic stimulation

due to inflammatory conditions such as viruses, blood parasites, post-immunization, etc; see increased numbers of reactive lymphocytes

lymphosarcoma/lymphocytic leukemia

see more lymphoblasts +/- abnormal lymphocytes; see prominent, large nucleoli, and lacey chromatin

lymphopenia/lymphocytopenia

decreased numbers of circulating lymphocytes

- lymphocytes are in tissue or body cavities (chronic high levels of glucocorticoids (stress, Cushing's), recirculation is disrupted (Chylothorax and Lymphomas), lymphosarcoma)

- bone marrow is not producing lymphocytes (viral infections (Feline Panleukopenia, Parvo), toxins, drugs (chemotherapy drugs), neoplasia in the bone marrow)

What are some causes of Lymphopenia/Lymphocytopenia?

monocyte

largest leukocyte; production time of 2-4 days in bone marrow but immature when released into circulation

macrophages or dendritic cells

When monocytes move into tissues or body cavities that become either:

macrophage

free or fixed; found in essentially all body tissues and survival in tissues varies from days to months

dendritic cells

antigen presenting cell

bone marrow

Macrophages do not have a storage pool in:

- irregular, lacy/reticulated chromatin pattern

- variably shaped, round, oval, kidney bean, multiple indentations

What does the nucleus of a monocyte look like?

- grey to blue-grey

- abundant

- prominent vacuoles that vary in number and size

- has inclusions (contain phagocytosed particles or whole cells occasionally)

How do the cytoplasms of monocytes appear?

phagocytosis and antigen presenting cell

What is the function of monocytes as macrophages?

phagocytosis

"big eaters"; process used by macrophages to engulf and destroy organisms that can't be controlled by neutrophils (such as fungi, protozoa, intracellular organisms, and some bacteria); used to remove debris from damaged areas and ingest dead/spent cells

antigen presenting cell

function used by macrophages to recognize and process foreign antigens that ten presents the antigen to the lymphocytes

monocytosis

increased # of monocytes in blood

- *chronic infection or inflammation

- recovery phase of an acute process

What does monocytosis indicate?

monocytes

Necrosis and cellular debris are chemotactic (chemically attractive) to:

- granulomatous inflammation (macrophages trying to wall off an insult they can't get rid of such as tuberculosis or brucellosis)

- in dogs as response to stress or corticosteroid administration

When do we see monocytosis?

monocytopenia

decreased # of circulating monocytes

- during acute stages of infection or inflammation

- with corticosteroid administration in some species

When does monocytopenia occur?

little clinical significance

Since the normal count of monocytes is minimal, monocytopenia is of:

neutrophil

What is the most numerous leukocyte in the peripheral blood of a feline?

lymphocyte

What is the most numerous leukocyte in the peripheral blood of a bovine?

polymorphonuclear

A neutrophil can also be known as a PMN. What does PMN stand for?

thymus

What part of the lymphatic system do the T-cells mature?

- histamine

- antigen-antibody complexes

- proteins of inflammation and allergies and may help play a role in regulating those responses

What are eosinophils attracted to?

eosinophils

activated by most parasites (especially migrating parasites), attach to a parasite and degranulate; this process along with the presence of antibodies, will kill the organism

- minor phagocytic ability

- can detoxify some chemicals

- play a role in coagulation by activating steps in the clotting mechanism

- circulate on demand

What are the functions of eosinophils?

- nucleus: lobular and segmented

- cytoplasm: pink to orange-red granules

What is the morphology of eosinophils?