When the initiating injury is slow, immunity is slow to awaken
A host of etiologies evoke chronic, not acute inflammation. Some infections, metabolic products, autoimmune reactions etc. are slow to be recognized by the immune system. Instead of the classical neutrophil response in acute inflammation, in chronic inflammation it is mononuclear and takes time. The net result – a long latent period passes as this slow response gathers momentum to liberate cytokines and damage tissues significantly to produce localizing symptoms and signs or systemic reactions like fever, malaise and weight loss. The slower the evolution, more protracted the course, more extensive the damage, longer the requirement for therapy and, not least, more morbid the outcome with long lasting damage to structure and function.
Insights and Impact
- Chronic Inflammation is slow in onset and prolonged in duration
- Clinically, the initial symptoms are mild/often absent, bringing the patient later to medical attention
- Innocuous or indolent etiologic agents (infectious or non-infectious; exogenous or endogenous in origin) elicit a delayed immunologic response of the mononuclear type.
- This determines the lack of/or minimal symptoms, locally and systemically, for a prolonged latent period
- The course of the illness is long, characterized by exacerbations – resultant scarring that impairs structure and function (e.g., tubercular pleural scarring impedes expansion of the lung affecting respiratory function; in chronic forms of arthritis joint distortion affects functional movements etc.)
- Diagnosis is challenging, often involving a range of laboratory and radiologic investigations. Once established surrogate blood markers assist in monitoring response to therapy
- The cornerstone of management: elimination of the etiology, management of the immune reaction and its systemic manifestations; sometimes, surgical intervention: to remove a lesion in entirety and/or its consequences (scarring)
- Physician-Patient communication must emphasize the likely long duration of multidrug therapy, uncertain outcomes or disability, significantly determined by patient’s ownership of three key actions, fundamental to recovery: patience, compliance with therapy and good nutrition
- Depending upon the localization of disease, physiotherapy may be required for rehabilitation
- Mental health support of the patient and caregivers is an often neglected but vital aspect of management
Rhythm ‘n Rhyme
Slow, persistent and destructive: beware chronicity
When the enemy creeps in slowly and the body is slow to respond
Chronic inflammation with its etiology develops a special bond;
Swift and active neutrophils no longer roll the dice
Macrophages and lymphocytes twirl a tango, the affected organ pays the price;
If close to the skin or mucosal surfaces, blind-ended sinus openings can be seen
Fistulas connect with bowel loops: their tell-tale contents yellow-green;
When the inflammation is organized, granulomas develop discrete masses
If cheesy suspect Tuberculosis, when solid think of other etiologic classes;
But the body has been endowed with wondrous healing ways
Growth factors call in new cells, to enter the inflammatory fray;
When damaged tissues are labile, regeneration can still be complete
When damage is significant or in stable tissues even healing or repair is a feat;
The ECM ‘glue’ scaffolds regeneration-repair with fibers and matrix
It links with epithelial cell receptors to regrow and tissues fix;
Local and systemic factors influence the ultimate outcome
Many fortunately will heal but unwelcome complications are the fate of some;
Management is protracted and complex, medical and surgical options abound
Patient-physician plain-speak and patience make outcomes sound…
Deep Dive
Examples of consequences of chronic inflammation
- Sinus and Fistula (microscopically, diffuse forms of chronic inflammation)
Acknowledgement of Image:
https://in.pinterest.com/pin/408138784976246364/
In (a) hair shafts embedded in the blind tract (pilonidal sinus) leading from the skin into the subcutaneous tissues, act like a foreign material, sustain a chronic inflammatory response and delay healing. In (b) the colo-cutaneous fistula containing leaking fecal material connects a bowel loop with skin and has openings in both, the persistent, chronic inflammation of its walls delaying healing.
Q. Think about the etiology of these two conditions and a comprehensive management approach using medical and/or surgical options.
B. Granuloma (microscopically, a focal form of chronic inflammation)
Acknowledgement of Image:
https://upload.medbullets.com/topic/104040/images/tuberculosis_granuloma_blog.jpg
A characteristic tubercular granuloma: the chronic mononuclear inflammatory infiltrate organizes itself into a mass (=oma). At the center, transformed macrophages – epithelioid cells (plump and pink due to abundant cytoplasm providing enhanced phagocytic and digestive capability) and multinucleate giant cells (arrow), enable Mycobacterial elimination. A mantle of lymphocytes collars the epithelioid cells and collaborates with them in the immune reaction. Due to persistent and slow chronic inflammation, organized into a granuloma, fibrosis begins at the periphery.
Not seen in this image is the structureless, cheesy, central necrosis called caseation, a hallmark of tubercular granulomas.
Q. The relatively indolent mycobacteria remain trapped, and sometimes viable, in the centers of granulomas. How does this understanding of the pathogenesis of granulomas impact management protocols and expected cure?
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