1. Mucoid swelling (Initial phase)
Mucoid swelling is a superficial and, crucially, reversible phase of disorganization.
The pathogenesis is based on the accumulation and redistribution of acidic glycosaminoglycans (formerly called mucopolysaccharides). These substances are hydrophilic: they actively bind water and sodium ions. Against the background of increased vascular permeability, this leads to marked hydration and swelling of both the ground substance and collagen fibers (they lose their resistance to collagenase).
Microscopic picture:
- On hematoxylin and eosin staining, foci of glycosaminoglycan accumulation exhibit basophilia.
- Staining with toluidine blue reveals the phenomenon of 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, yet their function is already impaired. The detection of such foci (most commonly in vessel walls and the endocardium) signals the onset or exacerbation of a disease. 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 the ground substance occurs alongside a significant increase in vascular permeability.
Fibrinoid forms within the tissue—a complex substance composed of collagen breakdown products, ground substance components, blood plasma, and cellular nucleoproteins. An essential component of fibrinoid is fibrin (formed from fibrinogen with the participation of tissue thrombokinase).
Morphology of fibrinoid:
- Light microscopy: with standard hematoxylin and eosin staining, fibrinoid appears as homogeneous eosinophilic masses. The exception is systemic lupus erythematosus, where an admixture of chromatin imparts a basophilic hue to these masses.
- Electron microscopy: accumulations of fibrin and disrupted 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 in the most severe alterations and leads to a drastic reduction or complete cessation of organ function (e.g., the development of acute kidney injury in lupus nephritis).
3. Immunopathological reactions
The morphological picture of disorganization is closely related to types of hypersensitivity reactions that succeed one another as the disease progresses:
- Immediate-type hypersensitivity (Type I, II, III reactions): Dominate at the onset of the disease or during exacerbations. Characterized by alterative and vascular-exudative changes. The tissue shows plasmatic imbibition, mucoid and fibrinoid swelling, up to fibrinoid necrosis. 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 are formed. Productive vasculitis develops, wherein intimal and adventitial cells proliferate to such an extent that the boundaries of the vessel wall are obliterated.
4. Sclerosis (Final phase)
Sclerosis is the final stage of connective tissue disorganization. The process is systemic in nature, but most pronounced in serous membranes, vessel walls, and cardiac membranes (endocardium, myocardium, pericardium). Sclerosis develops as a predictable unfavorable outcome of preceding cellular reactions (granuloma formation) and fibrinoid changes, leaving a permanent structural trace in the affected organ.
Briefly: answers to topical questions
Which enzymes are involved in the destruction of the ground substance and fibers during connective tissue disorganization?
The sources indicate two enzymes associated with connective tissue alterations during its disorganization:
- Hyaluronidase — its activation leads to the weakening of the bond between glycosaminoglycans and protein in the ground substance.
- Collagenase — during mucoid swelling, collagen fibers swell, and their resistance to collagenase decreases.
The abbreviation MFS will help remember the stages of disorganization: Mucoid swelling (reversible) → Fibrinoid changes (point of no return) → Sclerosis (final outcome, scar).
Class and exam questions
What causes metachromasia in mucoid swelling?
By the accumulation of acidic glycosaminoglycans, which change the color of the dye (toluidine blue) from blue to lilac or red.
Which component is an essential part of fibrinoid?
Fibrin. It is formed from blood plasma fibrinogen under the influence of tissue thrombokinase in the focus of injury.
How do fibrinoid masses appear on hematoxylin and eosin staining?
Typically homogeneous eosinophilic (pink) masses. The exception is systemic lupus erythematosus, in which they acquire a basophilic hue due to an admixture of disintegrating chromatin.
What does the development of fibrinoid necrosis lead to?
Irreversible reduction or complete cessation of organ function (e.g., acute kidney injury) with subsequent outcome in sclerosis or hyalinosis.
What else to study on this topic
- Mechanisms of increased vascular permeability in immunopathological processes
- Features of fibrinoid changes in systemic lupus erythematosus (SLE)
- Morphology of granulomas in delayed-type hypersensitivity reactions
- Differences between sclerosis and hyalinosis as outcomes of fibrinoid changes
- Pathogenesis of acute kidney injury development in lupus nephritis
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