1. Mucoid Swelling (Initial Phase)
Mucoid swelling is an initial and, crucially, a reversible phase of disorganization.
The pathogenesis is based on the accumulation and redistribution of acidic glycosaminoglycans (formerly known as mucopolysaccharides). These substances are hydrophilic: they actively bind water and sodium ions. Amid increased vascular permeability, this leads to marked hydration and swelling of both the ground substance and collagen fibers (making them lose their resistance to collagenase).
Microscopic appearance:
- On hematoxylin and eosin (H&E) staining, foci of glycosaminoglycan accumulation exhibit basophilia.
- Toluidine blue staining demonstrates metachromasia—a shift in dye color to lilac or red.
- A cellular reaction develops in the tissue: macrophages, lymphocytes, and plasma cells appear.
Macroscopically, organs are virtually unchanged, although their function is already impaired. The detection of such foci (most commonly in vessel walls and the endocardium) signals the onset of disease or its exacerbation. If the process is not halted, it progresses.
2. Fibrinoid Changes (Irreversible Phase)
The second phase—fibrinoid swelling—is characterized by profound and irreversible damage. Destruction of fibers and ground substance occurs against a background of significantly increased vascular permeability.
Fibrinoid forms within the tissue; this is a complex complex comprising collagen breakdown products, ground substance components, blood plasma proteins, and cellular nucleoproteins. An obligatory component of fibrinoid is fibrin (formed from fibrinogen with the participation of tissue thromboplastin).
Morphology of fibrinoid:
- Light microscopy: On standard H&E staining, fibrinoid appears as homogeneous eosinophilic masses. An exception is systemic lupus erythematosus (SLE), where chromatin admixture imparts a basophilic hue.
- Electron microscopy: Accumulations of fibrin and destroyed collagen fibrils that have lost their characteristic cross-striation are visualized.
The outcome of this stage is either sclerosis/hyalinosis or fibrinoid necrosis. The latter occurs during the most severe alterations and leads to a sharp reduction or complete cessation of organ function (e.g., the development of acute kidney injury in lupus nephritis).
3. Immunopathological Reactions
The morphological pattern of disorganization is closely linked to hypersensitivity reaction types that succeed one another as the disease progresses:
- Immediate-type hypersensitivity (Type I, II, III reactions): Predominant at the onset of the disease or during exacerbations. Characterized by alterative and vascular-exudative changes. Plasmatic imbibition, mucoid swelling, and fibrinoid swelling up to fibrinoid necrosis are observed in the tissue. The process is accompanied by thrombosis, hemorrhage, and infiltration by polymorphonuclear leukocytes and macrophages.
- Delayed-type hypersensitivity (Type IV reactions): Succeed immediate-type reactions. Cellular (proliferative) reactions come to the forefront. Lymphohistiocytic infiltrates and granulomas form. Productive vasculitis develops, in which intimal and adventitial cells proliferate to such an extent that the boundaries of the vessel wall are obscured.
4. Sclerosis (Terminal Phase)
Sclerosis is the final stage of connective tissue disorganization. The process is systemic, but most pronounced in serous membranes, blood vessel walls, and cardiac membranes (endocardium, myocardium, pericardium). Sclerosis develops as a predictable unfavorable outcome of preceding cellular reactions (granuloma formation) and fibrinoid changes, permanently leaving a structural mark on the affected organ.