Leukocyte abnormalities Flashcards
(31 cards)
Differentials for neutrophilia
Inflammation
Stress of steroid therapy
Excitement (catecholamine release)
Granulocytic leukaemia
Paraneoplastic
Leukocyte adhesion deficiencies (e.g. Irish setters)
Inflammatory neutrophilia
Acute inflammation (can continue for prolonged period) -> release of inflammatory mediators -> increased release of segmented neutrophils from storage pool in bone marrow
If rate of release is higher than emigration from circulation to tissue it is neutrophilia
If more marked can see band neutrophils
Chronic inflammation - neutrophils more likely to reach full maturity before release as bone marrow adapted
Causes of acute inflammatory neutrophilia
Infection
Immune mediated
Neoplastic disease
Necrosis
Most marked in dogs and pigs, less so in cats, horses, and cattle.
Left shift
An increased number of circulating band neutrophils.
These immature cells are released by the bone marrow, usually in response to increased demand for neutrophils associated with acute inflammation.
The nucleus of band neutrophils has no indentation that is more than 1/3 the width of the maximal diameter of the cell.
Toxic changes
Morphological changes in neutrophils that occur in strong inflammatory responses (usually infectious diseases) that are associated with accelerated granulopoiesis.
Examples of toxic changes
Dohle bodies
○ Blue dots in cytoplasm of neutrophils that are aggregates of RNA.
○ Low numbers can be seen in the neutrophils of normal healthy cats.
Increased cytoplasmic basophilia (blueness)
Cytoplasmic vacuolation
Toxic granulation (especially cattle)
Giant neutrophils
Doughnut nuclei
Chronic inflammatory neutrophilia
Granulocytic hyperplasia has occurred - neutrophil production should meet the increased demands so it is mature cells that are released
Can also be associated with a monocytosis, lymphocytosis, eosinophilia and sometimes right shift
Right shift
Increased numbers of hypersegmented neutrophils in the circulation.
Hypersegmented neutrophils have >5 lobes and represent older cells.
These older cells can be present in chronic inflammatory responses, or can be seen in animals treated with steroids (since steroids prevent adhesion and migration of neutrophils into the tissue).
Inflammatory neutrophilia in cattle
Limited storage pool therefore no or minimal neutrophilia in response to infection.
Often neutropenic in acute inflammation (consumption of circulating neutrophils).
Neutrophilia secondary to stress or steroid therapy
Release of endogenous glucocorticoids secondary to stress and hyperadrenocorticism, or exogenous steroid therapy can cause neutrophilia due to redistribution of neutrophils from the marginating to the circulating neutrophil pool (fall off walls of blood vessels) and increased release of neutrophils from the bone marrow storage pool.
Usually only twice the upper limit or less (cats can be higher)
Stress leukogram: mature neutrophilia (no left shift), lymphopaenia, monocytosis, eosinopaenia
Normal c-reactive protein or SAA
Differences between acute inflammatory neutrophilia and chronic inflammatory neutrophilia
Acute inflammatory neutrophilia
Usually left shift
No monocytosis
+/- lymphopenia
+/- eosinopenia
No right shift
Chronic inflammatory neutrophilia
Left shift less common
+/- monocytosis
+/- lymphocytosis
+/- eosinophilia
No right shift +/- right shift
Differences between chronic inflammatory response and stress leukogram
Chronic inflammatory response
Mature neutrophilia (no left shift)
+/- Lymphocytosis
Monocytosis
+/- Eosinophilia
Elevated serum C-reactive protein or SAA
Stress leukogram
Mature neutrophilia (no left shift)
Lymphopenia
Monocytosis
Eosinopenia
Normal C-reactive protein or SAA
Neutrophilia associated with excitement (catecholamine release)
Catecholamines cause the movement of mature neutrophils from marginating to circulating pool - cats have bigger MNP so get a bigger response
More common in healthy animals, and esp cats
Short lived response - neutrophil count normalises within an hour
Mild lymphocytosis
How to differentiate catecholamine induced neutrophilia from inflammatory repsonse
Lack of monocytosis in catacholamine induced
No left shift
Granulocytic leukaemia
Uncommon cause of neutrophilia - will be marked
Appear morphologically normal
Caused by neoplastic proliferation of granulocytic precursors in bone marrow
Diagnosis made after exclusion of other causes of leukaemoid response
May see infiltration of liver/spleen/LNs with granulocytic precursors
Chronic cases can progress to ‘blast crisis’ - maturation of cells is arrested resulting in neutropaenia - bone marrow heavily infiltrated so also see anaemia and thrombocytopaenia
Paraneoplastic neutrophilia
Various tumours can release cytokines such as G-CSF which will stimulate neutrophil production and maturation leading to a neutrophilia and sometimes a left shift.
The neutrophilia will resolve following treatment or removal of the tumour.
Leukocyte adhesion deficiencies
Marked neutrophilia, but as a result of neutrophil dysfunction or other problems with immunity, the neutrophilia is not effective in controlling infection and animals usually succumb to severe bacterial infections such as bacterial pneumonia.
In the dog leukocyte adhesion deficiencies are described in Irish Setters, and they have also been identified in Holstein cattle.
They are caused by defects in CD18, a receptor needed for neutrophil adhesion and migration into tissues.
Neutropaenia causes
Marked inflammation (and overwhelming demand)
Reduced production
Sedation
Lower in sighthounds generally
Inflammatory neutropaenia
Occurs in severe inflammatory diseases such as metritis, pyometra or inflammation of large organs or large surface areas.
Rate of emigration of neutrophils from the circulation into the tissue exceeds the rate of release of new neutrophils from the bone marrow
Associated with infections with Gram negative bacteria which cause endotoxaemia, because endotoxins stimulate the release of cytokines which cause margination and adhesion of neutrophils to the endothelium.
Since inflammatory neutropenia is secondary to marked inflammation, usually left shift and toxic changes will also be seen.
This sort of inflammatory neutropenia is common in cattle due to the small size of their marrow neutrophil storage pool.
Neutropaenia secondary to reduced production
This will be associated with hypoplasia of the marrow
might occur secondary to:
· Toxins (e.g. oestrogen – contraceptive pill)
· Chemotherapy
· Infections (e.g. FeLV, parvovirus)
· Myelopthsis of marrow (secondary to neoplasia or myelofibrosis
Differentiate from inflammatory neutropaenia by lack of left shift anf toxic changes
Cycilc haematopoeisis
This is a rare cause of neutropenia seen in grey collie dogs.
Defective stem cell proliferation leads to cyclic fluctuation of all cell lines out of synchrony with one-another.
The fluctuation in neutrophil numbers is the most dramatic, resulting in an episodes of severe neutropenia lasting 2 - 4 days, occurring every 12 days.
Causes of lymphocytosis
Chronic inflammation
○ + Neutrophilia.
○ + Monocytosis.
○ +/- Left shift and toxic changes.
Excitement (catecholamine release)
○ Neutrophilia.
○ Mild elevation (2x RI).
Young animals post vaccination
Lymphoma/leukaemia
Hypoadrenocorticism
May also see eosinophilia
Lymphocytosis with chronic inflammation
Lymphocytosis of chronic inflammation occurs in response to chronic antigenic stimulation which in turn leads to lymphoid hyperplasia.
Lymphadenopathy may also be seen.
Chronic inflammatory lymphocytosis may be associated with a neutrophilia (mature or with left shift [if marked]), monocytosis and possibly eosinophilia.
Lymphocytosis with excitement
This occurs due to movement of lymphocytes from the marginating lymphocyte pool to the circulating lymphocyte pool in response to catecholamines.
This lymphocytosis is usually rapid (normalising within a few hours) and is usually mild (up to twice the upper end of the reference interval).
Excitement induced lymphocytosis may also be associated with mature neutrophilia.
