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Clin Path
Leukocytes
38
Veterinary Medicine
Graduate
02/07/2012

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Term
Leukogram basics:
Definition
-Leukogram: measurements and data on a CBC that describes the leukocytes in the blood
-Leukocytes: all WBCs including neutrophils, eosinophils, basophils, monocytes, and lymphocytes
-philia and cytosis describe an increase in the concentration of certain cells in the blood
-penia describes a decrease in the concentration of certain cells in the blood
Term
Describe neutrophil production:
Definition
-hematopoietic cells originate from a common pluripotent stem cel
-pluripotent stem cells give rise to more differentiated stem cells that have capacity to mature into granulocytes (i.e. neutrophils, eosinophils, basophils) and monocytes
Term
List the progression of the sequence of neutrophil production:
Definition
Myeloblast->progranulocyte->myelocyte-> metamyelocyte-> band neutrophil->segmented neutrophil
Term
How do developing neutrophils appear as they mature?
Definition
-become smaller
-nuclear chromatin condenses
-nuclei become progressively more elongated and segmented
Term
How long does it take for transit from myeloblasts to segmented neutrophils? How does this change during disease?
Definition
-(6-7) days in health

-under conditions of increased stimulation and demand (e.g. inflammation and demand (e.g. inflammation) this transit time can be shortened (2-5 days)
Term
What regulates neutrophil production and release?
Definition
-Numerous cytokines (e.g. IL-1, IL-3, IL-6, GM-CSF, G-CSF, TNFalpha, TNFbeta, C5a, PAF, LTB(4)
Term
List the three neutrophil pools.
Definition
1. Marrow pools
2. Blood pools
3. Tissue neutrophil pools
Term
What does the marrow pool consist of and describe the components?
Definition
1. Proliferation pool: consists of myeloblasts, progranulocytes, and myelocytes. These cells are mitotically active (i.e. undergoing cell division)
2. Maturation and storage pools: consists of metamyelocytes, band neutrophils, and segmented neutrophils. Cells in these pools no longer undergo cell division.
Term
What do the blood pools consist of and describe the components?
Definition
1. Circulating pools: consits of neutrophils freely flowign in the vasculature. This is the pool measured on a CBC**
2. Marginated pool: consists of neutrophils that are "rolling" along and loosely adhered to endothelial surfaces via adhesion proteins (selectins)

**These two pools are in dynamic equilibrium and neutrophils can go from one pool to the other
**The marginated pool: circulating pool ration is approximately one in domestic mammals. This ratio is approximately three in cats.
Term
What does the tissue neutrophil pool consist of?
Definition
Neutrophils that have migrated into tissues(do not return to circulation
Term
***REVIEW A DIAGRAM OF THE CELL LINES***
Definition
Term
The maturation/storage pools serve as resevoirs for neutrophils to be released into circulation. How does this reservoir differ among dogs, ruminants, cats, and horses
Definition
-largest in dogs
-smallest in ruminants
-intermediate in cat and horse
Term
Which species have the greatest capacity to produce neutrophils (with ruminants on the other end of the spectrum) and therefore have more capacity to respond to an increased peripheral demand for neutrophils compared to ruminants?
Definition
Dogs

Dogs>cat,horse>ruminants

*larger animals have smaller pools and proliferative capacity
Term
Neutrophils are released from maturation/storage pools into circulation with the most mature cells being released first (i.e. segmented neutrophils). What happens under conditions of increased demand (e.g. inflammation)?
Definition
-more immature forms (i.e. band neutrophils, and rarely metamyelocytes) can be released into circultion
Term
What happens to neutrophils in circulation?
Definition
Can migrate to sites of inflammation or in health, are lost via apoptosis or transmucosal migration (primarily in the respiratory tract and GI tracts)
Term
What is the half life of neutrophils in circulation?
Definition
Six hours
Term
When and why does a left shift occur?
Definition
-when increased numbers of band neutrophils are present in circulation
-typically the result of depletion of segmented neutrophil storage pool within the bone marrow, causing a release of more immature forms
-these immature forms are usually band neutrophils, but rarely, even more immature forms such as metamyelocytes or myelocytes can be seen
Term
What does a left shift signify?
Definition
Often the result of a significant inflammatory stimulus and is considered the HALLMARK OF ACUTE INFLAMMATION (acute/ongoing demand)
Term
What is the difference between regenerative and degenerative left shifts?
Definition
-Regenerative: seg neutrophils > non-seg neutrophils (bands)
-Degenerative: seg neutrophils < non-seg netutrophils (bands)
Term
Characteristics of degenerative left shifts.
Definition
-"worse prognosis"
-interpretation is somewhat different between small animal and large animal due to differences in neutrophils reserves and proliferative capacity of the bone marrow (**VERY IMPORTANT TO UNDERSTAND)
Term
Small animal degenerative left shift vs. Large animal
Definition
-SA: worse prognosis b/c if have deg. left shift have depleted large pool (bad)
-LA: deg left shift is more common b/c have smaller pools
Term
Describe the general mechanisms of neutrophilis:
Definition
-shift from marginated pool to circulating pool (minutes/hours)
-increased release from the maturation/storage pools in the bone marrow (hours)
-increased production by bone marrow (days)
Term
List causes of neutrophilia:
Definition
1. inflammation
2. steroid neutrophilia
3. epinephrine neutrophilia
4. neoplasia-Chronic granulocytic leukemia-Rare
5. paraneoplastic-tumor production of G-CSF
6. Other-leukocyte adhesion deficiency
Term
Describe inflammation as a cause of neutrophilia.
Definition
-can be due to numerous underlying causes such as infectious (e.g. bacterial, fungal), immune-mediated disease (IMHA), necrosis, hemorrhage, neoplasia, etc
-a left shift is often present (but not always)
-mechanisms? increased release from marrow, increased production by precursors in marrow
Term
Describe steroid neutrophilia as a cause of neutrophilia.
Definition
-results from increased amounts of endogenous or exogenous glucocorticoids (e.g. stress, glucocorticoild therapy, Cushing's dz)
-mechanisms: shift from marginated to circulating pool, increased release from bone marrow
Term
Describe epinephrine neutrophilia as a cause of epinephrine.
Definition
-due to effects of catecholamines (fear, strenuous, exercise, excitement)
-neutrophilia is transient (resolves within an hour)
-most often seen in cats and young horses
-mechanisms: shift from marginated to circulating pool
Term
List general mechanism of neutropenia.
Definition
-shift from circulating to marginated pool
-decreased production within the bone marrow
-overwhelming tissue demand
Term
List causes of neutropenia
Definition
1. inflammatory neutropenia
2. Endotoxemia
3. decreased production
4. periphral destruction (rare)-Immune-mediated neutropenia. Autoimmune disease characterized by the presence of antineutrophil antibodies.
Term
Describe inflammation as a cause of neutropenia.
Definition
-most often seen in cattle with acute inflammation because relatively small storage pools, smaller proliferative capacity
-a left shift is often present (but not always)
-mechanisms? overwhelming tissue demand
Term
Describe endotoxemia as cause of neutropenia.
Definition
-infection with gram- bacteria can cause an endotoxemia
-mechanism: shift from circulating to marginal pool
Term
Describe decreased production as a cause of neutropenia.
Definition
-due to damage of granulocytic precursors or bone marrow microenvironment (e.g. viruses, tick-borne diseases, drug reactions, chemotherapeutics, neoplasia/leukemia, myelofibrosis)
-mechanisms: decreased production of neutrophils in bone marrow
Term
Under which circumstances would morphological toxic change in neutrophils occur?
Definition
-changes occur in developing neutrophils within the bone marrow during times of increased production
-as such, toxic change is often associated with inflammatory conditions (e.g. bacterial infectious, immune-mediated disease, etc)
-toxic neutrophils have normal functions
Term
List morphologic toxic changes seen in neutrophils.
Definition
1. cytoplasmic vacuolization-dispersed organelles
2. cytoplasmic basophilia-increased cytoplasmic RNA
3. Dohle bodies-focal cytoplasmic basophili/inclusions. Represent aggregates of rough endoplasmic reticulum ***note: healthy cats can have small numbers of Dohle bodies
4. giant neutrophils-asynchronous maturation, rarely seen
5. toxic granulation-staining of primary granules. Rarely seen (horses)
Term
List infectious agents that may be present in neutrophils.
Definition
1. Bacteria-Morulae of Anaplasma and Ehrlichia species
2. Histoplasma capsulatum-yeast phase of organism
3. Distemper inclusions-red to pale blue cytoplasmic inclusions (can also be seen in monocytes, lymphocytes, and erythrocytes)
4. Protozoa-Hepatozoon sp, Toxoplasma sp
Term
What is Pelger-Huet anomaly?
Definition
-inherited abnormality of neutrophils
-occurs in several breeds of dogs, DSH cats, and Arabian horses
-All granulocytes (neutrophils, eosinophils, basophils) have hyposegmented nuclei
-Nuclei are band to oval-shaped with a mature appearing chromatin pattern
-neutrophils have normal function
-what is the clinical significance? if dog has deg left shift but clinical signs (BAR, jumping up and down, could be Pelger-Huet anomaly)
Term
What is Chediak-Higashi syndrome?
Definition
-rare
-described in cats (Persian), cattle, and other mammals (mink, whale)
-characterized by large eosinophilic cytoplasmic inclusions (lysosome fusion)
-Neutrophil function is somewhat abnormal, however, animals are generally healthy
-animals also have a slight tendency to bleed due to abnormal platelet function
Term
What is Birman cat neutrophil granulation?
Definition
-rare-fine eosinophilic cytoplasmic granules within neutrophils
-function is normal
-cats are healthy
Term
What are mucopolysaccharaides?
Definition
-rare
-puruple to magenta colored cytoplasmic granules within neutrophils
-caused by deficiency of specific lysosomal enzymes
-animals often have other developmental abnormalities
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