SAM.HI2: Leukocyte Disorders

Neutrophils in the bone marrow exist in 2 forms

mitotic (myeloblast, promyelocyte, myelocyte).

storage (metamyelocyte, bands, segmenters).

A left shift indicates (2)

active inflammation.

absolute number of bands >300/uL.

A degenerative L shift

nonsegmented exceed the segmented.

The presence of blast is concering for

granulocytic leukemia - rare to see mitotic cells in circulation in severe inflammatory response.

Stress causes release of

marginal neutrophils into circulation as well as increased release from the bone marrow storage pool.

Stress response in the dog

neutrophils can reach 40k.

lymphopenia.

eosinopenia.

monocytosis.

Stress response in the cat

Neutrophilia - may not be as pronouned.

Monocytosis may not be seen.

Fear, excitement, and stress in ctas

significant neutrophilia and lymphocytosis - via NE release.

Leukemoid rxn occurs w/

Neutrophils between 50k-100k.

result of inflammation.

Leukemoid rxn can be seen w/ what processes (4)

immune-mediated dz.

some infection.

paraneoplastic phenomenon.

neutrophil fxn'l defects.

Leukemoid responses lack

the prominent blasts seen w/ leukemia.

Leukomoid responses commonly have

L shift and evidence of toxicity

Leukoerythroblastic rxn occurs when

both immature erythroid and myeloid cells are found in circulation.

Leukoerythroblastic rxn is seen w/ (4)

bone marrow dz.

splenic hemangiosarcoma.

hemolytic anemia.

significant blood loss.

Basic causes of Neutropenia (6)

Normal - variation of normal for the individual.

Infection.

Inflammation.

Bone Marrow.

Immunodeficiency.

Autoimmune.

Basic causes of Neutrophilia (7)

Inflammation.

Infection.

Necrosis.

Neoplasia.

Autoimmune.

Leukemia.

Immunodeficiencies.

Idiopathic or immune-mediated peutropenia is

extremely uncommon and typically occurs in young dogs (rare in the cats.

Immune-mediated neutropenia - Secondary (3)

Drugs.

Infection.

Other immune mediated dzs - polyarthritis, ITP, and IMHA.

Drugs that can cause secondary IMN (4)

Pheno.

Ivermectin.

Methimazole.

Sulfas.

CS of IMN (7)

may be related to underlying dz or vague.

Signs related to spesis and infection.

leth.

fever.

lymphadenopathy.

splenomegaly.

GI signs.

Dx of idopathic IMN - blood (3)

severe persistent neutropenia <1500 on 2 occasions in the absence of other causes of neutropenia.

Bands are low or absent.

Occasional affected platelets.

Dx of IMN - Other Dxs

Bone marrow analysis.

Flow cytometry.

Bone marrow analysis in Dx of IMN

variable w/ myeloid hyperplasia in most (hypoplasia on some)

Flow cytometry in Dx of IMN

will identify Ab's, but not differentiate idiopathic from secondary

IMN tx

Tx secondary infection/underlying dz.

Immunosuppression + adjuncts.

Which adjunct is avoided w/ IMN

Azathioprine - bone marrow suppression

Relapse w/ IMN

common - often need for chronic management.

Splenectomy can be done in refractory cases but often not needed.

Pelger-Huet Anomaly is a

benign congenital disorder of granulocytes and monocytes that affects dogs and cats

Common breeds affected by Pelger-Huet Anomaly

Australian Shepherds/cattle dogs.

(Basenjis.

Border Collies.

Bostons.

Cockers.

Coonhounds.

Foxhounds.

GSD.

Samoyed.

DSH).

Pelger-Huet Anomaly: Defect is believed to be in

gene for lamin B - membrane receptor that interacts w/ chromatin and determines nuclear shape.

Genetic inheritance of Pelger-Huet Anomaly

Homozygous - die in utero.

Heterozygous - hyposegmented, variably shaped nuclei containing mature, coarsely, and densely clumped chromatin (look like bands but have mature chromatin pattern).

Pelger-Huet Anomaly: defect is in

terminal granulocyte maturation - thus granulocytes are fxn'l

Pelger-Huet Anomaly may present w/

degenerative L shift, but w/o the toxic changes expected in presence of illness.

Pelger-Huet Anomaly: Other young WBC lines (myelocytes and metamyelocytes) may be seen as well, but their

chromatin pattern is clumped (normal) v. the coarse pattern typically seen in affected cells

Tx for Pelger-Huet Anomaly

None - not clinical

Chediak-Higashi Syndrome is seen in

smoke blue [ersoams

Chediak-Higashi Syndrome inheritance

rare autosomal recessive

Chediak-Higashi Syndrome is the result of a

mutation in the LYST gene - regulates lysosomal trafficking w/in cells by encoding a protein that encodes membrane fusion.

Chediak-Higashi Syndrome: Result of mutation is an (4)

inadequate release of neutrophils from the bone marrow.

Decreased chemotaxis.

Reduced motility and decreased phagocytic capacity.

defective platelet aggregation.

Chediak-Higashi Syndrome: Associated abnormalities (2)

Oculocutaneous albinism w/ a lighter than normal coat.

Ocular abnormalities due to fusion of melanin granules.

Chediak-Higashi Syndrome: ocular abnormalities includes (4)

photophobia.

pale yellow, yellow-green, or green irises.

cataracts

decreased pigmentation of fundus.

Chediak-Higashi Syndrome: Clinical Manifestation (2)

increased susceptibility to infection (b/c the same mutation impairs NK cells).

prolonged bleeding time (due to abnormal platelet granules).

Chediak-Higashi Syndrome: presumptive Dz

compare the hair shaft of an affected blue smoke cat to an unaffected cat - melanin granules are large and clumped in the affected cat.

Trapped Neutrophil Syndrome is seen in

border collies

Trapped Neutrophil Syndrome: inheritance

autosomal recessive disorder - mutation in the vesicle protein sorting 13B gene

Result of Trapped Neutrophil Syndrome

Neutropenia, degenerative L shift, and monocytosis w/ myeloid hyperplasia.

Trapped Neutrophil Syndrome: Affected puppies are

small.

develop vxn rxn.

recurrent infection.

secondary immune mediated dz (polyarthropathy).

develpomental abnormalities - narrow, long skull and narrow limbs

Cyclic Hematopoiesis: seen in

gray collies

Cyclic Hematopoiesis: inheritance

autosomal recessive associated w/ color dilution (defect affects melanocytes).

Cyclic Hematopoiesis: mutation

insertional mutation in the AP3B1 hene - plays a role in systhesis of melanosomes, platelet granules, and lysosomes.

Cyclic Hematopoiesis: pluripotent cells in the bone marrow are affects causing abnormalities in (5)

neutrophils.

eosinophils.

monocytes.

platelets.

reticulocyte numbers.

Cyclic Hematopoiesis: Affected animal have

severe neutropenias q12-14d that last 2-3d and may result in infection.

Often rebound neutrophilia between episodes that lasts about 1wk.

Cyclic Hematopoiesis: Shifts are seen in other cells but nor with the same

schedule due to longer half lifes - often not as severe

Cyclic Hematopoiesis: Neutrophil fxn may be

abnormal w/ reduced neutrophil elastase and myeloperoxidase activity.

Cyclic Hematopoiesis: As a result of recurrent infection (2)

Imgb levels are increased.

systemic amyloidosis can occur in young animals.

Cyclic Hematopoiesis: Result of defect

most die by 6m of age.

Cyclic Hematopoiesis: What has been used to control dz

recombinant canine stem cell factors and G-CSF (limited avaiability

Birman Cat Neutrophil Granulation Anomaly: inheritance

Autosomal recessive trait in Birman cats

Birman Cat Neutrophil Granulation Anomaly: manifestation in cells

cytoplasm of Neutrophils contains numerous dark pink to purple small granules even in maturity.

Birman Cat Neutrophil Granulation Anomaly: Tx

neutrophils fxn normally so no tx neccessary

Canine X-linked Severe Combine Immunodeficiency (Canine X-linked SCID) is seen in what breeds

Cardigan Welsh Corgis and Bassets.

Canine X-linked SCID: mutation is in

gene for gamma chain of multiple interleukins receptors - so lymphocytes fail to respond to cytokines and T lymphocytes fail to develop.

Canine X-linked SCID: The defect is on the

X chromosome - females have a second X that can produce normal protein so they are spared.

Canine X-linked SCID: affected animals have

minimal to low number of T cells.

Poor T cell response to mytogens and blastogenesis.

Canine X-linked SCID: B cell lines (3)

B lymphocytes are increase.

IgG is low.

IgA is absent.

Clinical manifestation of Canine X-linked SCID (3)

lymphopenia.

hyperglobulinemia.

lymphoid hypoplasia of nodes and thymus - thymus is non-existent and lnn undetectable.

Canine X-linked SCID: Result of infection (2)

males fail to grow and develop recurrent infection.

most dogs die by 4m of age.

Immunodeficiency of Shar Peis: Clinical manifestations (3)

Decreased IgM and IgA levels.

Decreased proliferation.

Decreased blastogenesis and response to mitogens.

Immunodeficiency of Shar Peis" Onset

late - shows signs at about 3yrs.

Immunodeficiency of Shar Peis: CS include (5)

Pyoderma.

Demodicosis.

M. canis infection.

Pneumonia.

Intestinal dz.

Selective IgA deficiency: Seen in

GSD

Selective IgA deficiency: dogs are prediposed to

fungal infection.

pyoderma.

furunculosis.

SI dz.

Selective IgA deficiency: Imgb conc (2)

Normal IgG and IgM.

IgA is low.

Selective IgA deficiency: IgA problem is a result of a problem w/

synthesis or secretion of IgA (normal presence of plasma producing cells)

Lysosomal Storage Dz (LSD) are characterized by

enzyme deficiencies that allow the accumulation of metabolic intermediated w/in a cell's lysosomes.

LSD is commonly dx in

young animals w/ signs relating to abnormal growth.

LSD: organ systems affected are most commonly

MSK and CNS

LSD: Dx is made by

identifying the accumulation of these abnormal substances w/in cells via cytology or histo.