Hematology: Leukocyte Abnormalities Flashcards
Terminology
neutrophilia/neutropenia
eosinophilia/eosinopenia
basophilia
monocytosis
lymphocytosis/lymphopenia
leukocytosis/leukopenia
Physiological response
mild mature neutrophilia, lymphocytosis, +/-monocytosis
Secondary to epinephrine release
short-lived–>resolves after 30 min
young animals (<1 year)
Stress response
mild to moderate mature neutrophilia (up to 2x upper reference), lymphopaenia, eosinopaenia +/- monocytosis
Endogenous or exogenous corticosteroids
Neutrophils from BM storage pool and marginated pool –> circulating pool
lasts ~24 hours, longer if prolonged steroid exposure
Inflammatory leukogram
mild to marked neutrophilia, lymphopaenia, and monocytosis
presence of left shift or toxic change
magnitude of changes depend on:
- duration
- severity of inflammation
- nature of inflammation
- species of animal
Left shift
if demand is high, than immature forms of neutrophils are released from the bone marrow
Regenerative left shift: neutrophilia with mainly mature neutrophils with some immature forms seen
Degenerative left shift: more immature forms than mature neutrophils; neutrophil count may be normal, mildly raised or reduced
Leukaemoid reaction: very high neutrophil count with strong left shift.
Toxic change
marked inflammation (esp. bacterial infections) marked tissue necrosis
due to direct toxic effect on neutrophil progenitors in the bone marrow and also the immaturity of cells being released into blood.
Left shift
Dohle bodies in neutrophils (inclusions-remnants of rough ER)
Increased cytoplasmic basophilia (RNA)
Cytoplasmic vacuolation (also happens if in EDTA for too long)
Toxic granulation
Cell and nuclear swelling
Giant neutrophils, ring forms (rare)
Species differences
Cats and dogs capable of marked neutrophilias >horses >ruminants
Ruminants typically see neutropenia in initial stages of inflammation- cattle don’t have big storage pool of neutrophils.
Horses may also see neutropenia acutely esp. if endotoxemia. endotoxins lead to margination of neutrophils. if gut barriers break down–>endotoxins–>margination of neutrophils (nb: can also see circulating pool of n’phils with blood test)
Peracute, severe, overwhelming inflammation: neutropenia in cats and dogs (uncommon)- be very concerned if you see this
Neutrophilia
increased number of circulating neutrophils
occurs with:
excitement/physiological (mild)
stress/corticosteroids
inflammation
rarely with granulocytic leukemia
Neutropenia
deficiency of circulating neutrophils
cattle: transient neutropenia in acute inflammation
other species:
-severe, overwhelming inflammation
toxic depression of bone marrow: toxins/drugs (bracken, chemo tx), infectious agents (feLV), neoplasia or myelodysplastic syndromes
immune-mediated (rare/contraversial)
Clinically important as increase risk of infection (particularly bacterial infection).
Eosinophilia
increased number of circulating eosinophils
occurs in response to IL-5 released by T-cells+histamine release by mast cells.
Parasitic conditions
Allergic/hypersensitivity
paraneoplastic (uncommon):cancer stimulates production of eosinophils—mast cell disease, lymphoma (cancer of lymphoid cells), various other neoplasms (rare).
Eosinopaenia
deficiency of circulating eosinophils
endogenous or exogenous steroids inhibit mast cell degranulation and neutralize histamine
eosinopaenia by itself is of little diagnostic significance.
Monocytosis
increased circulating monocytes
excitement/physiological
stress/exogeneous corticosteroids (dogs)
inflammation
monocytic leukemia (rare)
Monocytopaenia- not recognized- reference interval is close to zero.
Lymphocytosis
increased number of circulating lymphocytes
physiological (excitement)
may occur in infectious disease, during recovery or in chronic disease
post vaccination in young animals
lymphoid neoplasia
lymphopaenia
deficiency of circulating lymphocytes
occurs in infections: viruses, septicaemia
stress: endogenous and exogenous corticosteroids; transient altered distribution of lymphocytes between blood and lymphoid tissue.
Hematopoietic Neoplasia
blood cancer
clonal proliferation of heatopoeitic progenitor cells: one stem cell has gone rogue and divides and proliferates uncontrollably
results from accumulation of mutations of that cell’s DNA
sometimes specific agents are involved:
retroviruses: FeLV, BLV, ALV
herpesviruses e.g. marek’s disease, burkitt’s lymphoma
Tumour groups include: leukemia, plasma cell tumours, mast cell tumours, lymphoma, histiocytic disease
Lymphoma vs. lymphoid leukemia
Lymphoma: very common type of neoplasia coming from lymphoid tissue (LN)- spill out into blood eventually
Leukemia: kicks off in the bone marrow. neoplastic cells can spill into the blood
Can be difficult to differeniate between these two.
Leukemia
primary site in the bone marrow. moves from marrow into the blood and from there can secondarily infiltrate into tissue
Maturation and functional defects: some are very immature and don’t function properly.
can be diagnosed on routine hematology but sometimes need a bone marrow exam.
normal blood sample: normal little buffy coat (WBCs and platelets) sitting above RBCs
leukemic blood sample: massively expanded buffy coat.
Classification of leukemia
Degree of maturation of cells involved: acute- reactive, big, blast cells; chronic-cells more mature
mirrors clinical picture and progression of disease
Presence or absence of neoplastic cells in the blood: no neoplastic cells being released into blood=subleukemic leukemia (aleukemic)
Lymphoid: B cell or T-cell
Myeloid: erythroid, granulocytic, monocytic, megakaryocytic; can see mixed lineages.
Consequences of leukemia
Myelophthisis: replacement of bone marrow population by neoplastic cells–healthy BM encroached upon and overrun by cancer cells
EMH: extramedullary hematopoeisis–> EMH results in splenomegaly/hepatomegaly (also because cancer cells can infiltrate other organs)
Hemodynamics: if very high WBC, blood is thicker and can impair blood flow through microvasculature– certain areas of body can suffer from hypoxia–>CNS signs, even cardiac impairment.
Acute leukemia
Acute undifferentiated leukemia, acute lymphoblastic leukemia, acute myeloid leukemia
At any age, but often seen in younger animals
aggressive disease: present acutely and often very sick
immature blast cells in the circulation
most are thrombocytopaenic and anaemic, sometimes pancytopenia (reducing of all WBCs–> indicates that myelophthisis is occuring)
Histopath presentation of acute leukemias
acute lymphoblastic leukemia: immature cells seen: immature lymphocytes (lymphoblasts) with nucleoli, basophilic cytoplasm, larger than mature lymphocytes.
in acute myeloid leukemia: see blast cells of myeloid lineage
some special stains can highlight myeloid vs. lymphoid lineage.
nb: some cats (burmese) have some pink granules in neutrophils.
Clinical signs of acute leukemia
Lethargy, anorexia, weight loss
Pyrexia (neutropenia–>infection), shifting limb lameness
Bleeding from mouth/nost, melaena (bleeding into upper intestinal tract)
Neurological signs (hypoxia d/t blood character)
On PE may find: spleno/hepatomegaly; mild generalized lymphadenopathy (enlarged LNs), petechiae/echymoses (slightly larger than petechiae) due to thrombocytopenia.
Chronic leukemia
chronic lymphocytic, chronic granulocytic, polycythemia vera (i.e. increased red cells being produced (primary absolute polycythemia- not EPO-directed))
older animals
slow onset, progresses slowly
can be asymptomatic
neoplastic cells are well-differentiated i.e. mature cells in circulation
may see mild non-regenerative anemia but generally other cells lines are unaffected
Histopath presentation of CLL
small, mature lymphocytes, some neutrophils, not encroaching on marrow’s ability to make WBCs.
