Thursday, February 23, 2012

Granulomas Redux...What are they again?

As you know, I have been addressing the granuloma question in some detail.   Had lots of questions so I thought it might be appropriate to address in more detail.  From the perspective of the hip, a granuloma may come into play as a reaction to the high levels of toxic metals in the body.  A small portion of the hip population is reported to have these ( less than 1%) but  most of the time, no one would know they are present unless they are discovered by accident through some unrelated radiology procedures or scan.  Honestly, I question that low incidence of these granulomas.

1.  Granulomas remain enigmatic. 

·         While they  have been studied extensively, much is unknown about them.  They are also hard to define.   Defining a granuloma is difficult.  In the orthopedic community, one might call a granuloma a pseudotumor of which there are hundreds of articles written on the occurrence of these with hip artheroplasty (both initial and revised procedures.)

2.  What are granulomas and what is their purpose?

·         A granuloma,

o   In its simplest form is an inflammation characterized by the presence of lymphocytes (white blood cell ), monocytes (Monocytes are a type of white blood cell) and plasma cells .  It is is a medical term for a tiny collection of immune cells known as macrophages. The role of a macrophage is to phagocytose (engulf and then digest) cellular debris and pathogens.  Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate it.....like perhaps metals.

o   In a complex form can be defined as a collection of mature mononuclear phagocytes which may or may not be accompanied by necrosis.

·         One of the basic functions of the granuloma is to rid the host of unwanted substances…like metals or a million other things.  The introduction of a foreign substance into the host evokes acute inflammation.  Leukocytes engulf the invader and attempt to destroy it.  When their attempt is successful, the inflammation resides.  If not, the invader comes to lie within mononuclear phagocytes.  The continued presence of the invader, especially in a particulate form and in high concentration may stimulate mononuclear phagocytes to mature, coalesce and divide.  A mature granuloma results.  If the intruder and its components are particularly stimulatory or if delayed sensitivity develops, the macrophages mature even further to epitheloid cells.  The resultant epitheliod granuloma persists until the foreign intruder is destroyed.  Then the lesions slowly resolve as the mononuclears die, revert to less mature forms or wander off.

3.  The tempo at which granulmatous inflammation develops can vary considerably and depends upon the inciting agent and the state of the host.  The lesions can grow in as few of as 3 days.  The further development into epiteliod lesions require 22 days.  The accumulation and number of epitheloid cells are accelerated in hosts displaying strong delayed hypersensitivity to the evoking agent.

4. High turnover granulomas induced by relatively toxic substances  proliferate briskly.  The natural history of high-turnover granulomas is to develop into low turnover lesions as the inciting agent is degraded.  The granuloma itself persists until the inciting agent is destroyed.  The constituent macrophages could have several possible ends:  division, emigration or death.

5. One certain property needed for the granuloma development is the persistence of the evoking agent.  Granulomas persist only so long as does the inciting agent.  Some hypersensitivity-mediated granulomas require the agent to be in particulate form.  A high local concentration of a given agent is more likely to evoke a granuloma. 

5.  In summary:  Agents which evoke granulomas are likely to be persistent, particulate substances that are capable of producing modest maturation of macrophages.  Under appropriate circumstance, mature granulomas can evolve into epitheloid lesions, a change representing intensification of maturation.  The two processes are similar metabolically and morphologically and both are reversible after removal of the stimulant.  The presence of the granuloma does signify that a foreign substance has resisted destruction by the acute inflammatory response and is being sequestered and destroyed by mature elements of the mononuclear phagocyte system.  This is the body’s primary defense mechanism to foreign substances that are not welcome.

Delayed hypersensitivity can however greatly augment and accelerate the development of mature granulomas.
6.  Necrosis accompanies many granulomas.  In many cases the development of the delayed hypersensitivity to the intruder produces necrosis.  Factors other than hypersensitivity produce necrosis. 


 Prior posts that covered this topic:
Seeking information.......Granulomas, histiocytosis, type IV immune response.... (part 1 of x in this series)

So what is the cause of these pseudotumors after the second revision? (part 2 of x in this series)

Granulomas, necrotic pseudotumors post revision.....what is the story on this? (part 3 of x)

Background on Type IV Immune response (part 4 of x)

Background on Type IV Immune response (part 5 of x)

Background on Type IV Immune response (part 6 of x)

Connie's status with her investigation into tumor type growths (7 of x)

Granuloma journal articles provided to my medical Team related to the hip (8 of 8)

hope this post helps!

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