Leukon #4: Quantitative Response to Disease Flashcards
Neutrophilia - Physiologic
=Response to catecholamine release -Immediate onset ~30 minute duration -Causes: --Excitement --Exercise --Convulsions --Parturition -May be present with a concurrent lymphocytosis, together or as a sole change (young cats)
- Pattern:
- -Mild neutrophilia (neutrophilia < 2x URI or < 3x URI in cats)
- -No left-shift (storage pool is NOT affected)
- -Mild lymphocytosis
- -Erythrocytosis (splenic contraction)
- -Thrombocytosis (splenic contraction)
- -Hyperglycemia (related to epinephrine effects, multifactorial)
Neutrophilia - Glucocorticoid Stress
- Exogenous (therapy)
- Endogenous (stress, hyperadrenocorticism)
- Neutrophil source - storage and marginal pools
- Timing - effects within a few hours (3-5 hours)
- -Duration:
- –Length of stress
- –Half-life of drug
- Not going to see many bands, if any
- Pattern:
- -Mild neutrophilia (neutrophilia < 2x URI < 3x URI in cats)
- -Little or no left-shift
- -Lymphopenia (HALLMARK)
- –Consistent across species; corticosteroids trap lymphocytes in lymphoid organs
- -+/- monocytosis (common in dogs, less so in cats)
- –Inconsistent across species
- -+/- eosinopenia (consistent between species)
- –Gets stuck in the bone marrow
- -Hyperglycemia (related to cortisol effects on insulin, glycogen, lipolysis, etc.)
- -Increased ALP activity (dogs ONLY)
Neutrophilia - Inflammation (dog, cat, and horse) - General Info
- Infectious: bacteria, viral , fungal, parasites
- Non-infectious: burns, infarction, immune-mediated, necrosis, trauma, surgery, and toxicosis
- Greatest neutrophilia is seen in association with conditions that are “walled-off”: abscess, pancreatitis, pyelonephritis, prostatitis, closed pyometra, IMHA, etc.
Neutrophilia - Acute Inflammation
- Increased tissue demand for neutrophils is MET by mobilizing the storage pool
- -Mitotic pool has not had time to respond
- Moderate neutrophilia with left shift (seg < 30-35 k/uL)
- -Toxic changes common
- -Stress is common - lymphopenia
- -Tissue demand for macrophages is common - monocytosis
- Pattern:
- -Leukocytosis characterized by neutrophilia
- -Regenerative left-shift (release of storage pool)
- -Toxic changes are likely (shortened maturation and accelerated release)
- -Monocytosis: may or may not be present if there is increased tissue demand for macrophages
- -Lymphopenia is expected because of concurrent glucocorticoid stress (sick animal)
Neutrophilia - Chronic Inflammation - Early
- Expanded BM, but strong left shift indicates lack of balance with tissue demand
- Segs > 35,000 = expansion
- Toxic changes, stress, tissue demand for macrophages are common
- Pattern:
- -Leukocytosis characterized by neutrophilia
- -Strong left shift (release of storage pool)
- -Toxic changes are common (shortened maturation and accelerated release)
- -Monocytosis is common
- -Lymphopenia is common because of concurrent glucocorticoid stress (sick animal)
Neutrophilia - Chronic Inflammation - Late
- BM expanded - lack of bands (or minimal number)
- Production has balanced with the demand
- Pattern:
- -Mature neutrophilia (met demand)
- -No or minimal left shift (met demand)
- -Monocytosis is common
- –Typical interpretation: inflammation with increased tissue demand for macrophages
- This stage is difficult to differentiate from early acute inflammation with no left shift
- Sequential CBC as well as history of chronic conditions are helpful to determine it
- As production meets/exceeds needs –> resolution phase
- Mature neutrophilia gradually decreases toward reference interval
- -Typical: neutrophilia, no left shift, +/- monocytosis
- Classic = neutrophilia with monocytosis
- -Safest response = inflammation with tissue demand for macrophages
- -Likely process = chronic inflammation
- –Cannot rule out early acute (no left shift) with tissue destruction (not chronic just because of the monocytosis, it’s the pattern)
- –Sequential CBCs and/or history of chronic condition is helpful
Neutrophilia - Chronic Inflammation - Leukemoid Response
- Leukemia-like based on numbers and left shift
- Marked leukocytosis (>50,000)
- -Majority segmented neutrophils
- -Left shift back to metamyelocytes and potentially myelocytes
- -“Orderly” left shift (segs > bands > metamyelocytes > myelocytes)
- Pattern:
- -Marked leukocytosis characterized by marked neutrophilia (>50,000 /uL)
- -Marked left shift (bands, metamyelocytes, myelocytes): left shift is “orderly” with higher numbers of more mature stages
- Support for benign:
- -Orderly left shift
- -Lack of atypical/dysplastic cells
- -Finding inflammatory nidus (pyometra, prostatic abscess, pancreatitis, etc.)
- Support for leukemia:
- -Early precursors and segs without intermediate precursors
- -Increased atypical or dysplastic cells
- -Lack of inflammatory nidus
-Bone marrow follow-up if unclear
Neutropenia - Excess Demand
- Overwhelming inflammation
- -Strong tissue demand - storage and maturation pool
- –Depletions BEFORE mitotic pool increase
- –Toxicity often present
- –Causes:
- —Bacterial infections, endotoxemia (salmonellosis in horses)
- —Acute viral (parvovirus in dogs, cats)
- Pattern
- -Leukopenia
- -Neutropenia (excessive tissue demand)
- -Degenerative left shift (anytime there are more bands than segs) - intended to convey very critical finding
- -Neutropenic with degenerative left shift –> critical
- -Normal neutrophil with degenerative left shift –> serious, monitor
- -Neutrophilic with degenerative left shift –> less serious, BM responding
Neutropenia - Excess Peripheral Destruction
- Immune-mediated neutropenia (peripheral destruction)
- -Rare condition
- -Increased susceptibility to infections
- -Consider for persistent, unexplained neutropenia
- -Mitotic –> storage pools are increasing, but circulating –> tissue pools are decreasing
Neutropenia - Decreased Production
- Drug reactions (chloramphenicol in cats, phenylbutazone, cephalosporins, griseofulvin)
- -Anti-cancer, antibiotics, antimycotics, estrogens, NSAIDS
- Infectious (viruses - FeLV, FIV, parvo; rickettsia; systemic mycoses)
- Toxicoses (bracken fern, estrogens)
- Genetic (cyclic hematopoiesis)
- Myelophthisis (i.e. crowding)
-All pools decreased
Neutropenia - Ineffective Production - Dysgranulopoiesis
- Myelodysplasia
- Immune-mediated
- -Directed at marrow level
- -Could be directed at different stages in mitotic pool and maturation pool
Neutropenia - Increased Margination
- Slowed circulation (anesthesia/shock)
- Pools = inverse of physiologic
- Next, increased egress into tissues leads to patterns of:
- -Acute inflammation (neutrophilia with LS)
- -Excess tissue demand (neutropenia with LS)
- Transient phase, often too early to see clinically (peracute)
Inflammatory response in ruminants - Adults
-Small storage pool
- Typical acute inflammation:
- -Neutropenia with left shift and lymphopenia from stress
- –Not overwhelming, just acute
- –Prognosis of pattern better than in others (dog, cat, horse)
- –Last 24-48 hours –> normal neut + LS –> mild neutrophilia + LS
- Typical chronic inflammation:
- -Neutrophilia with left shift + toxicity (marrow expansion)
- –10,000 - 20,000 neut = very significant
- –>20,000 neut = rare
- Fibrinogen may be earlier, more consistent inflammatory marker
- -Acute phase protein
- -Produced in the liver
- -Present in plasma
- -Forms fibrin clots
Inflammatory response in ruminants - Calves
For first 3-4 months, inflammatory response is like a dog or cat
- If >/= 4 months, consider as adult leukogram
- Neutropenia with LS = overwhelming inflammation
- -Serious or guarded prognosis
Eosinophilia
- Sites affected: mast cell rich tissues (esp. skin, lung, GI, uterus)
- Parasitic (endoparasites or ectoparasites with tissue phase/exposure)
- Allergic/Hypersensitivity (a type of inflammation)
- -Asthma, eosinophilic bronchopneumopathy
- -Allergic dermatoses (+/- bacterial component: staph, strep)
- -Eosinophilic granuloma
- Neoplasia - eosinophilic leukemia (IL-5: mast cell, T-cell lymphoma, carcinomas (pulmonary))
- Hypoadrenalism (Addison’s) (<20% of patients)