Granulomatosis with Polyangiitis

Etiology and mechanisms of development

The exact etiological cause of this disease remains unclear to this day and is a subject of scientific debate. It is believed that specific antigens of undetermined nature act as the initial triggering factor. The mucosa of the upper respiratory tract serves as the portal of entry for these pathogenic agents, where the very first pathological processes unfold.

The pathogenesis of the disease is based on complex immunopathological reactions. The leading mechanism of damage to the body's own tissues is closely associated with the aggressive effects of immune complexes circulating in the blood as well as locally fixed ones. Their deposition in the vascular wall triggers a potent cascade of inflammatory reactions, resulting in a pronounced granulomatous reaction. In addition, the patient's genetic predisposition plays a crucially important role in the development of the pathology: the occurrence of the disease has been reliably proven to be associated with the carriage of certain major histocompatibility complex antigens, specifically such markers as HLA-B7, HLA-B8, and HLA-DR.

Morphological and histological picture

The morphological and structural basis of the disease is severe systemic necrotizing vasculitis. Unlike many other vascular pathologies, in Wegener's granulomatosis the inflammatory process has a pronounced productive character and is always accompanied by the formation of specific cellular granulomas. Small and medium-sized blood vessels are predominantly involved in the pathological process, affecting both the arterial and venous vascular beds.

Detailed microscopic examination of the affected tissues reveals a complex and diverse cellular composition of the developing granulomas. They are formed by dense accumulations of lymphoid cells, monocytes, active macrophages, and fibroblasts. However, the most important, specific histological feature enabling the pathologist to accurately verify the diagnosis is the mandatory presence of neutrophilic leukocytes in the inflammatory infiltrate, as well as pronounced signs of thrombovasculitis (acute inflammation of the vessel wall accompanied by the formation of an obliterating thrombus directly in its lumen).

Organ pathology: classic triad

The classic course of the disease is characterized by a strict and recognizable triad of lesions sequentially involving the upper respiratory tract, lung parenchyma, and the patient's kidneys.

• Upper respiratory tract and bronchial tree: Aggressive necrotizing granulomatosis develops on the mucosa of the respiratory tract. Macroscopically upon examination, this manifests as the formation of multiple deep ulcerations that gradually destroy the normal anatomical structure of the surrounding tissues.
• Lung tissue: Extensive focal-confluent changes form in the lung parenchyma, represented by zones of massive cellular infiltration and subsequent necrosis. Clinically and morphologically, the pathological process in the lungs most frequently presents as severe bilateral bronchopneumonia.
• Kidneys: Renal filter involvement is the third, yet equally important mandatory component of the classic triad. Patients develop glomerulonephritis, which upon histological examination of the biopsy is classified predominantly as a mesangioproliferative or mesangioproliferative/mesangriocapillary variant of nephritis.

Generalization of the process and complications

Despite the presence of the classic triad, this vasculitis is truly systemic in nature and has a high tendency toward generalization. The skin, central and peripheral nervous systems, visual organs, and joints may additionally be involved in the severe pathological process. Heart involvement represents a particular clinical danger, which can manifest as coronaritis (inflammation of the coronary arteries supplying the myocardium), severe myocarditis, or exudative pericarditis.

Complications of the disease are always extremely severe, disabling, and at times fatal:

1. ENT organ destruction: The progressive necrotic process naturally leads to the complete destruction of the nasal cartilaginous septum, visually manifesting as its pronounced and irreversible deformation. Against this background, secondary bacterial infections frequently join in, presenting as persistent purulent sinusitis and otitis.
2. Pulmonary hemorrhage: Acute cavities (decay cavities) eventually form in zones of extensive lung tissue necrosis. Purulent melting of blood vessel walls within these cavities becomes the direct cause of massive, life-threatening pulmonary hemorrhages.
3. Renal failure: Steadily progressive glomerulonephritis leads to the rapid decline of renal filtration function, ultimately ending in end-stage renal failure.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Detailed mechanisms of formation of circulating and fixed immune complexes in systemic vasculitis.
• Pathogenesis of the development of thrombovasculitis and its impact on the ischemia of surrounding tissues.
• Morphological and histological differences between mesangioproliferative and mesangiocapillary glomerulonephritis.
• Features of the formation of acute cavities in lung tissue and mechanisms of development of profuse pulmonary hemorrhage.
• Variants of cardiac involvement during the generalization of the process: morphology of coronaritis, myocarditis, and pericarditis.

Other topics in the section "Pathology of the Cardiovascular System"

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