Abnormalities of the leukon 1&2 Flashcards
How can WBCs be measured?
- machine: impedance and optical
- RBC lysed, nucleated cells stream through channel where electrical impedance or optical deflection noted
- accurate for total numbers
- machine: quantitative buffy coat (QBC)
- machine scans a spun down large PCV tube and relates fractions to where cell types settle
- problems with abnormal cells/ platelet enumeration
- differentials poorly performed
- manual methods: chamber counts/ unopette systems; not commonly used except for exotic /avian spp
- blood smear estimates: from monolayer, assuming no clots/ clumping, count number of leukocytes in a monolayer x100 field, divide by four, correlates roughly to WBC*10e9/L. Should average at least 10 fields to minimise variation across smear
What is included in the total WBC concentration?
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
What is the leukocytes differential?
- typically 100 consecutive cells
- ideally 100 cells/ 10*10^9/L
- e.g. 87% neutrophils
- neutrophil conc = [WBC] * %
Influences on total leukocyte numbers
- dynamic equilibrium
- centred on balance b/w peripheral demand and ability of BM to supply adequate replacements
- other factors include position of leukocyte within BV (marginated or circulating) and availability for sampling
What is CFU-G?
colony-forming-unit-granulocyte: a self-renewal stem cell
What in ProNP?
proliferation neutrophil pool
- contains myeloblast (Mb), progranulocyte (Pg) and myelocyte (Mc)’
- mitotic pool
- simlated by various factors
- apoptosis at myelocyte stage to limit production in health
- timeframe: about 3d
What is MatNP?
= Maturation Neutrophil pool
- metamyelocyte (Mmc), band neutrophil (B) adn segmented neutrophil (S)
- post-mitotic pool
- time: 2-3d (dogs)
- MatNP: ProNP ration = 4-6
What is CNP?
Circulating Neutrophil pool: what is sampled during blood collection
What is MNP?
Marginated Neutrophil Pool: ready to exit the circulation and migrate into the tissues (TNP - tissue neutrophil pool)
What is the CNP: MNP ratio?
near 1 (cats: 3)
What is the neutrophil half-life in blood?
5-10 hours
What is neutrophil left shift?
if demand high, more immature neutrophils are released (bands or earlier)
What is neutrophil toxic change?
- cytoplasmic foaminess and basophilia
- Dohle bodies
- giant neutrophils
- vacuolation
- toxic granules
Describe toxic neutrophils
- in peripheral blood
- accelerated production
- no need for toxins
Describe degenerate/ lytic neutrophils
- in tissues (fluids)
- fighting with bacteria
- bacterial toxins
Classifications of left shift
- REGENERATIVE LEFT SHIFT: neutrophilia, segmented > bands
- DENEGERATIVE LEFT SHIFT: neutropenia, bands > segmented
- in between?
- large vs. small animals
Causes - neutropenia (increased demand)
- peracute bacterial infections (e.g. peritonitis, pyothorax)
- endotoxaemia
- immune-mediated: alongside decreased neutrophil survival time
Causes - neutropenia (redistribution)
- in response to endotoxaemia, anaphylactic shock
- neutrophils undergo increased margination to vessel walls (fewer free to sample)
Outline neutropenia (decreased production)
- usually BM disorders
- INFECTION; parvo, FIV, FeLV, Ehrlichia
- TOXICITIES: commonly iatrogenic e.g. azathioprine, cyclophosphamide, idiosyncratic drug reactions
- INEFFECTIVE PRODUCTION: myelodysplasia (often FeLV related)
- CHANGE IN MARROW ENVIRONMENT: myelofibrosis, myelophthisis (crowding out by neoplasia)
- CONGENITAL ABNORMALITIES: cyclic neutropenia of grey collies, Chediak-Higashi syndrome (neutropenia in cats)
What is important to know about neutropenia?
- beware breed differences (greyhounds) and individual variation (if mild, track)
- CS are indirect
Therapeutic intervention - neutropenia
most give BS ABs if neutrophils
Causes - neutrophilia (increased production to increased demand)
- INFECTIONS: bacterial, viral, protozoal
- IM diseases: IMHA, PA etc
- secondary to neoplasia
- haemolysis, haemorrhage, necrosis, thrombosis
Causes - neutrophilia (increased production independent of demand)
- well differentiated neutrophils transformed: chronic granulocyte leukemia, numbers can be v high, rule out appropriate causes for increase
- poorly differentiated (early precursors) transformed: acute myeloid leukaemia, prognosis v poor
Outline neutrophilia d/t increased persistence in circulation
- stress/steroid response: neutrophils remain in circulation longer, more available to sample
- may be hypersegmented (been around long enough for extra segmentation to occur)
- accompanied by monocytosis and lymphopaenia (other steroid effects)
Outline neutrophilia d/t redistribution
- stress/ excitement increases BP
- marginated neutrophils not normally sampled swept of BV wall into circulation
- may increase WBC numbers up to 200% in cats
- lymphocytes prevented from leaving circulation/ mobilised from thoracic duct - numbers increase
Tx - neutrophil abnormalities
- tx underlying cause
- chronic granulocytic leukaemias: good short term prognosis
- acute myeloid leukemias: no successful tx
Outline differences in lymphocytes
- BC and TC look same
- BC mostly short-lived, days to wks, memory BCs and a few others longer lived
- TCs long lived (months to years)
- formed in BM but production and clonal proliferation in thymus, spleen, LNs
- can recirculate from blood into tissues, back via lymphatics, in and out of lymphoid tissue and back into blood
Location - leukocyte production
- BM (all cell lines)
- spleen and liver maintain potential to produce all WBC lines
- thymus, spleen, LNs, bursa of fabricius (birds): mostly differentiation of lymphoid
- complex interplay of growth factors
Causes - lymphopaenia d/t increased demand
- some PLE (loss of lymphocyte rich chyle)
- chylo-thorax/ peritoneum with drainage
- recruitment and emigration into tissue with some antigens
Causes - lymphopaenia d/t redistribution
- STEROIDS: endogenous (stress) or exogenous: redistribution to BM, tissues, trapping in LNs
- Trapping in lymph rich fluid (chylothorax)
Causes - lymphopaenia d/t decreased production
- INFECTION: virus (canine distemper, parvo, panleukopaenia, FeLV, FIV)
- LYMPHOLYTIC DRUGS: chemotherapeutics (e.g. cyclophosphamide, azathioprine, long-term corticosteroids)
- CONGENITAL IMMUNODEFICIENCIES(e.g. Bassett Hounds) where BC and TC affected
Causes - lymphocytosis d/t increased demand
- persistent Ag stimulaton (fungal, protozoal, FeLV, leishmania, brucellosis)
- post-vaccination
- young animals
Causes - lymphocytosis independent of demand
- chronic lymphocytic leukaemia (well-differentiated)
- acute lymphoblastic leukaemia (more poorly differentiated)
- Stage 5 lymphoma: BM involvement and release of neoplastic lymphocytes into circulation
Causes - lymphocytosis d/t redistribution
- physiological leukocytosis, inhibition of recirculation, release from TD
- hypoadrenocorticism (11-20%)
What are monocytes?
- monoblasts to monocytes in 6d
- no storage pool, don;t have marginated and circulating pools
- persistence in circulation varies (20h in cattle), shortens with inflammation
- leave circulation to tissues, differentiate into macrophages with inflammatory cytokines
Describe decreased monocyte cell numbers
Not recognised as a clinically separate entitiy
Causes - monocytosis d/t increased demand
- INFECTION: bacteria, fungal, protozoal
- IMMUNE-MEDIATED DISEASE: IMHA, meningitis, PA
- NECROSIS, trauma, burns
- Neoplasia
Causes - monocytosis independent of demand
- secondary to immune neutropaenia - common precurosis (CFU-GM)
- myelomonocytic leukaemia: acute or chronic
- acute mnocytic leukaemia: with or without maturation
What may cause monocytosis d/t redistribution?
Steroids may move monocytes out of the marginated pool
Tx - monocytosis
- tx underlying cuase
- chronic myelomonocytic much the same as chronic granulocytic
- no really successful tx for acute myelomonocytic leukemias in SA
Describe eosinophil lifecycle
- differentiate and mature in 2-6d (spp dependent)
- variable persistence in circulation (
Cause - eosinopaenia
- mechanism unclear:
- corticosteroids (endogenous or exogenous) via apoptosism possible neutralisation of histamine/ mast cell degranulation and other mechanisms
- catecholamines
Cause - eosinophillia d/t increased demand
- via sensitised TCs, mast cells: IL-5 release
- parasite Ag
- ‘allergic dz’: atopy, drug allergy, asthma, pulmonary infiltrate with eosinophils
- inflammation of MC rich tissue (gut, skin, lungs, uterus)
Causes -eosinophilia independent of demand
- PARANEOPLASTIC (lymphoma, MCT, others where IL-5 elaborated)
- HYPEREOSINOPHILIC SYNDROME -numbers increase in circulation, tissue w/o clear cause
- EOSINOPHILIC LEUKAEMIA - rare
Describe basophil lifecycle and role
- maturation and release from BM over 2.5d
- persist in circulation for 6h
- role in type 1 hypersensitivities: anaphylaxis, rhinitis, asthma, GI sensitivities, parasites
- ? role in delayed hypersensitivities
- poorly understood in most domestic spp
Causes - decreased numbers of basophils
possible with anaphylactic, inflammatory and steroid responses
How to detect decreased numbers of basophils
impossible to detect on normal blood screens - reference interval begins at 10 for most
Causes - basophilia d/t increased demand
- IMMEDIATE OR DELAYED HYPERSENSITIVITIES: drugs, food, insect bites/stings
- PARASITISM: especially dirofilaria, also GIT parasites, fleas and ticks
- OTHER INFLAMMATORY RESPONSES
Causes - basophilia independent of demand -2
- PARANEOPLASITC: especially MCT
- BASOPHILIC LEUKEMIA - rare
What is a stress leukogram?
= response to CORTICOSTEROID (endogoenous or exogenous)
- mild to moderate mature neutrophilia
- lymphopaenia
- monocytosis
- eosinophilia
What leukocyte response may be seen with Addison’s?
may get reverse stress leukogram:
- neutrophils and monocytes usually WNL
- lymphocytosis
- eosinophilia
- changes usually mild
Describe an acute inflammatory leukogram
- neutrophilia +/- left shift
- lymphopaenia
- monocytosis
+/- eosinopenia
Describe a chronic inflammatory leukogram
- neutrophilia +/- left shift
- lymphocytosis
- monocytosis
What is the leukocyte adrenaline response? 2
- neutrophilia
- lymphocytosis
Describe normal haemogram of young animals
- increased WBC #s
- lower Hct
- changes are mild and generally normalised by 3mo
