Neutrophils are the most common WBC.  Monitoring their numbers can serve as a good indicator of the stage and degree of an infection (see below).  Ordinarily, neutrophil production is around 100 billion/day.  Note that RBC production is only twice that of neutrophil production (200 billion RBC's produced/day).  Sometimes, people wonder why the number of RBC's in circulation is 800 times higher than the number of WBC's in circulation.  One of the reasons is because of the time that the cells actually spend in circulation.  RBC's spend 100-120 days in circulation while neutrophils spend only about 10 hours in circulation, after which they migrate in to the mucosal tissues.  Once a neutrophil moves into the tissues, it can survive for about 5 days, unless it is used to fight infection in which case it is immediately sacrificed!

Before we go any further... let's recall... RBC's spend up to 120 days in circulation, granulocytic WBC's spend about 10 hours in circulation, monocytes spend about 24 hours in circulation, platelets spend about 10 days (not hours, days) in circulation.  Lymphocytes can actually move back and forth between circulation and tissue.  While lymphocytes may also sacrifice themselves when attacking foreign agents in the body, lymphocytes can survive for months to years!

neutropenia = too few neutrophils

neutrophilia = too many neutrophils

The boxes in this diagram of PMN kinetics are compartments which can be assessed.  The easiest to assess is the circulating pool (CP) as the CP represents the PMN's in circulation; the ones you would collect in a blood sample!  Familiarize yourself with the compartments in the diagram before trying to interpret the material regarding changes in cell kinetics during infections found below!

PP = the proliferative pool - the proliferative pool is comprised of immature blast type cells, which have migrated to an appropriate tissue and are committed to multiplying and becoming neutrophils; these cells are dividing rapidly and are no longer pluripotential, they can only become neutrophils

RP = reserve pool - the reserve pool is not a physically different "place" than the proliferative pool; when cells enter the reserve pool, it simply means they stop dividing; cells "sit" in the reserve pool for about 6 days, but when needed they can be ready to leave the reserve pool within 3 days; there are 2 sub-compartments within the RP!  These are the MP₁ (maturation pool) and the SP (storage pool)

MP₁= maturation pool - cells which arrive in the maturation pool are immature... they are incapable of fighting infection; the maturation pool would contain cells such as the myelocytes, metamyelocytes and band cells; it takes cells entering the maturation pool  full day to reach the band cell stage and 3 days to fully mature

SP = storage pool - after cells have matured, they typically remain in the storage pool for about 3 days, although they can leave the storage pool faster if necessary

CVP = the cardiovascular pool - the cardiovascular pool can also be thought of as having 2 sub-compartments; the sub-compartments are the marginal pool (MP₂) and the circulating pool (CP)

i) MP₂ = marginal pool - the marginal pool is made up of cells which are sticking to the epithelial lining of the vessels (vascular epithelium); these cells are either entering or leaving the circulation; we say that cells which stick to the lumen of the vessel are "marginating." The blood vessel walls have "selectins" which help the marginating cells to stick to the vessel walls, and the WBC's have "integrins" which help them to actually pass through the vessel walls.  In the presence of infection circulating cells will marginate and quickly move into the tissues, particularly as capillaries increase in diameter and blood flow rate is reduced

ii) CP = circulating pool - the circulating pool contains the cells which are actively circulating in the bloodstream; note that PMN's are only present in the CP for about 10 hours; therefore, cells in the CP are replaced 2.5 times/day, and only about 2% of the WBC's are actually in the circulation at any given point in time.  Note that PMN's must pass through the capillary endothelium (MP₂) to get into, and later to get out of the CP

TP = the tissue pool - eventually, PMN's "marginate" & pass into the tissue pool, where they can survive for up to 5 days; cells which are needed to fight infection are actively used and die immediately!  PMN's are lost primarily to destruction through use at the mucosal surfaces of the lung and gut... the mucosa is often referred to as the PMN graveyard!

Normally, there is unidirectional movement of PMN's from PP -> MP₂.  There is bidirectional movement of PMN's between the MP₂ and the CP (ie. bidirectional movement within the CVP).  There is unidirectional movement of PMN's from MP₂ -> TP... that is, a PMN could not move from the tissue back into the bloodstream... and therefore, it could not directly transport infectious material back into the bloodstream!

Stress (for example, the stress associated with having a blood sample taken) or strenuous exercise can cause a shift of PMN's from the MP₂ to the CP and giving an apparent increase in the number of neutrophils in the CP.

When might we see a neutrophilia?

In theory, a neutrophilia could be associated with an increase in PMN production, a decrease in PMN use or an increase in the transfer of PMN's from the MP₂ to the CP, as seen in exercise or stress!

OK, we know enough about the PMN "compartments" and we are ready to have a look at how we can get information from the PMN populations!

What might you expect to see if you collected blood samples from a person with a mild bacterial infection? (let's think about the most common WBC type, the neutrophil)

If you collected a blood sample early in an infection (ie. in the acute stages of a mild bacterial infection), you would likely observe a neutropenia due to the loss of neutrophils to the tissues for phagocytosis of infectious particles.  By the time the clinical signs of the mild infection were showing, the PMN levels would likely be normal as PMN's have moved out of the SP in response to the loss of PMN's to the TP.  In fact, if enough PMN's move out of the SP, there may even be a bit of a neutrophilia.  There may be a slight increase in the number of immature PMN's present in the CP (1-2% of the PMN's in circulation) as a few cells may move out of the MP₁ earlier than usual.  This increase in the number of immature cells in the CP is known as a "left shift" (here, with mild bacterial infection, we are talking about a very minor left shift, if at all).

What might you expect to see if you collected blood samples from a person with a severe bacterial infection? (again, let's look at the most common WBC, the neutrophil)

If you collected a blood sample early in the infection (ie. in the acute stages of a severe bacterial infection), we would again see neutropenia associated with the rapid loss of PMN's into the TP.  The rate of PMN loss would be extremely high in a severe bacterial infection, so once you get past the acute stage and into the mid-stage of the infection, the PMN SP may be depleted.  As PMN's continue to move from the CP to the TP, a neutropenia is maintained.  Now, the MP₁ is called upon - ie. all WBC reserves are called upon, including pools which contain immature cells!  Some cells even less mature than band cells start to appear in the CP.  These very immature WBC types can be considered to have little functional value.  They have not matured to the point where they are capable of fighting infection!  This is a "degenerative left shift."  Neutropenia with a degenerative left shift is "life-threatening," meaning that the prognosis is "guarded."  The patient becomes dependent upon exogenous factors to fight the infection (isolation, cleansing, disinfecting, removal, antibiotics, etc.).  With recovery from severe bacterial infection, there is a "regenerative left shift."  During recovery, the bone marrow "kicks in" and produces enough PMN's to exceed PMN loss. During this time, you still see an elevated number of band cells (left shift) but the number of mature WBC types will gradually increase (thus, a regenerative left shift).  More noticeable, perhaps, than the blood works is that the regenerative left shift is accompanied by obvious "health" improvement (signs typically associated with the "defeat" of an infection, such as reduction of inflammation and loss of fever).  A regenerative left shift may be maintained for a long period of time following a chronic infection (ie. the body may continue to try to compensate and go into extreme neutrophilia).  Occasionally, a neutrophila is maintained for months following a severe infection.

Glucocorticoid therapy may lead to neutrophilia as an increased number of PMN's are released from the bone marrow and a decreased number move into the TP.  Remember, GC's reduce inflammation... and one of the routes by which they accomplish this effect is to reduce the number of neutrophils entering the tissue pool!  As cortisol (our principle glucocorticoid) is released during stress, neutrophilia may develop during periods of stress.

Eosinophil kinetics tend to follow the PMN kinetics, as outlined above, during infection.  However, eosinopenia occurs in response to stress or continuous exercise (increased RBC's, neutrophilia and eosinopenia) as eosinophils are lost from the CP to MP₂ with stress (or with glucocorticoid injection).  Thus, the eosinophil response to stress or exercise, as seen in the CP, appears opposite to the neutrophil and RBC response. Eosinopenia is seen in bacterial infections as the loss to the TP exceeds replacement by the bone marrow. Remember, neutrophils are normally far more numerous than eosinophils.  Eosinopenia is seen in infectious diseases of the skin, gut and lungs as eosinophils are rapidly lost to mucosal tissues (the PMN graveyard).

Quick Review:  Exercise and stress (cortisol/glucocorticoid) affect the numbers of a few circulating cell types... notably, RBC's and neutrophils increase in number, and eosinophils decrease in number.