Clin path 8: Neutrophilia and Neutropenia Flashcards
What are the main causes of neutrophilia?
- Stress (cortisol-mediated)
- Excitement or physiologic (epinephrine-mediated)
- Inflammation
Outcomes of stress neutrophilia
- storage pools release
- Marginal to circulating WBC
When does neutrophilia occur?
- In response to endogenous or exogenous corticosteriods
How long does a stress neutrophilia take to occur?
Hours to days
CBC findings that support a stress neutrophilia
- Mild neutrophilia
- no left shift
- lymphopenia (Best supporter)
+ or - monocytosis and eosinopenia
Chemistry findings associated with neutrophilia
- Hyperglycemia
- INcreased ALP (dogs only)
Why does neutrophilia cause hyperglycemia?
- Cortisol has effect on insulin and glycogen production
Why do corticosteroids lead to neutrophilia?
- They increase the rate of nature neutrophils release from bone marrow storage pools
- They down-regulate adhesion molecules on neutrophils making the marginal neutrophils into circulating neutrophils
Why does stress neutrophilia lead to lymphopenia?
Corticosteroids “trap” lymphocytes in the lymphoid organs
What is excitement neutrophilia?
- Occurs in response to epinephrine release
** Happens most commonly in young, healthy animals, especially cats and horses
CBC findings associated with excitement neutrophilia?
- Mild neutrophilia
- no left shift
- mild lymphocytes
- Erythrocytosis (splenic contraction)
- Thrombocytosis (splenic contraction)
Chemistry finding related to an excitement neutrophilia?
- Hyperglycemia
- Increased ALP (dogs only)
Why is there excitement neutrophilia?
- Epinephrine causes increased HR and BP so marginal neutrophils get “washed” off the walls and into circulation
- Marginal into circulating pool
How long does the onset of an excitement neutrophilia take?
20-30 minutes
What species are we most likely to see the highest excitement neutrophilia in?
CATS! they have the largest marginal pool of neutrophils
What is inflammatory neutrophilia?
- Most clinically relevant
- Bone marrow changes in production of neutrophils
- Can be from acute or chronic inflammation
—- Sometimes we can not definitively tell if it is acute or chronic
CBC findings associated with inflammatory neutrophilia?
- Neutrophil count >2x URL
- Concurrent elft shift
- Neutrophils in toxic stage
- Lymphocytosis suggesting chronic inflammation
- monocytosis
- hyperfibrinogenemia with a decreased PP:fibrinogen (LA ONLY)
Chemistry findings of inflammatory neutrophilia
- Hyperglobulenemia
- Hypoalbuminemia
- Glucose
What does a inflammatory neutrophilia chemistry finding of hyperglobulenemia suggest?
- Chronic inflammation
- antigenic stimulation
- lymphoid hyperplasia
What does inflammatory neutrophilia chemistry finding of hypoalbuminemia suggest?
Production of albumin by the liver is down-regulated with inflammation **Not a definitive support fo inflammation
Why does inflammatory neutrophilia occur?
With acute or chronic inflammation:
- Release of neutrophils from bone marrow maturation pool
- The bone marrow will continue to produce more neutrophils
- As the inflammation persists or the severity is greater the bone marrow will push out more and more immature neutrophils
- This can lead to circulation of bands and a significant left shift
What is a left shift?
an increased number of immature neutrophils in peripheral blood
What is a regenerative left shift?
- Moderate to mild
- Bone marrow is responding to tissue inflammation and releasing earlier neutrophils from maturation pool
What is degenerative left shift?
There are more immature neutrophils circulating than mature segmented neutrophils
- Bone marrow can not keep up with the peripheral demand for neutrophils
“Overwhelming inflammation” = Poor prognosis
What is granulopoiesis?
Production of nuetrophils
What is toxic change?
Increased granulopoiesis in the bone marrow can lead to maturation defects
- Observed in a blood smear
What does toxic change occur secondary to?
- shortened maturation time
- Toxic injury to maturing neutrophils in the bone marrow
Both caused by inflammation
What is a leukemoid response?
Neutrophil number (any/all types) >50,000/uL
- subtype of chronic imflammation
What are causes of leukemoid response?
IMHA
The “P’s”
Neoplasia
Hepatozoon infections
How does IMHA cause leukemoid response?
When severe anemia-induced hypoxemia leads to tissue necrosis/death
What are the “P’s”?
Pyometra, pyothorax, peritonitis, pylenonephritis, pneumonia
How does neoplasia lead to leukemoid response?
Having necrotic portions that has outgrown its blood supply
What can inflammation with neutrophilia look like?
- Normal neutrophil numbers + left shift
- Normal neutrophil numbers + neutrophil toxic change`
What does the magnitude of the neutrophillia reflect?
The severity of the inflammation response
What does the character/size of the left shift reflect?
the severity of the disease and the animals ability to manage it.
what is happening in acute inflammation neutrophilia?
marginal and storage pools go into circulation and tissues die to demand
- Bone marrow has not had time to respond yet
What is happening in chronic inflammation neutrophilia?
Neutrophil lineage increases production in response to tissue demands
What are the main causes of neutropenia?
- inflammation
- decreased production
- sequestration- a transient cause
What is neutropenia?
a decreased absolute number of neutrophils.
*** Predisposes animal to infection
What is inflammation neutropenia?
tissue demands for neutrophils exceeds numbers of neutrophils available in the bone marrow
CBC findings associated with inflammation neutropenia?
- RBC and platelets unaffected (if decreased this is not ur diagnosis)
+ or - : left shift, toxic change, lymphopenia
Chemistry findings associated with inflammation neutropenia?
Hypoglycemia due to sepsis
Why is there neutropenia? What does it lead to?
- Severe inflammation
- Tissue demand exceeding marrow supply of neutrophils
- within 2-3 days animal will succumb to infection
OR - Bone marrow will undergo hyperplasia
- neutrophil development can be shorted from 5-6 days to 3-4 in all species except ruminants
- In 3-4 days after hyperplasia neutrophil numbers will increase again but it will be too late
What is the different about inflammation neutropenia in ruminants?
-Ruminants have a smaller pool of storage neutrophils so it depletes quicker
- this allows for quicker onset of bone marrow hyperplasia
- Ruminates will have bone marrow hyperplasia before they reach the poor prognosis of “overwhelming” inflammation
- therefore better off
CBC findings of a ruminant with inflammation neutropenia
- neutropenia
+ or -: - mild to marked left shift
- lymphopenia
What is decreased production neutropenia?
decreased in neutrophils due to conditions that may inhibit or stop neutrophil development from bone marrow
CBC findings associated with decreased production neutropenia?
+ or -:
- Decreases in other lineages
- Presence of many immature blast cells that support acute leukemia
- identifiable infectious agents
What can cause decreased production neutropenia?
- Viruses
- Toxins
- Drugs
- Estrogen
- Myelophthisis
What is sequestration neutropenia?
Decrease in neutrophils die to a transient phenomenon with endotoxemia
- Exotoxin cause a rapid shift of neutrophil from the circulating to marginal
- Tissue inflammation with demand for neutrophils can occur at the same time.