User:PecMo/sandbox3

Fibrinoid necrosis is a pathological lesion that affects blood vessels, and is characterized by the occurrence of endothelial damage, followed by leakage of plasma proteins, including fibrinogen, from the vessel lumen; these proteins infiltrate and deposit within the vessel walls, where fibrin polymerization subsequently ensues.

Although the term fibrinoid essentially means "fibrin-like", it has been confirmed through immunohistochemical analysis and electron microscopy that the areas referred to as "fibrin-like" do contain fibrin, whose predominant presence contributes to the bright, eosinophilic (pinkish) and structureless appearance of the affected vessels.

The earliest documented identification of fibrinoid histological changes dates back to 1880, when it was questioned whether these histological changes resulted from the deposition of a fibrinous exudate, or the degeneration and breakdown of collagen fibers.

The term "fibrinoid" was introduced to describe these changes, because distinguishing fibrinoid from hyaline deposits posed a significant challenge, as both exhibit a similar appearance under standard light microscopy. This morphological similarity necessitated the use of specialized histological staining techniques, such as phosphotungstic acid hematoxylin and various types of trichrome stains, to facilitate the distinction of fibrinoid material. Because these stains possess the ability to highlight and identify fibrin, this led to the term fibrinoid, which means "fibrin-like", being used to describe the affected vessels.

Nevertheless, as early as 1957, fibrin was indeed identified within fibrinoid, and by 1982, this understanding had advanced, with many researchers recognizing fibrinoid as a complex structure primarily composed of fibrin interwoven with various plasma proteins.

A renal biopsy from a patient with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis reveals a lesion characterized by bright eosinophilia on H&E staining (yellow arrow, left) and intense red staining with trichrome (right), confirming the presence of fibrinoid necrosis.

An H&E micrograph showing (intensely pink) fibrinoid necrosis (large blood vessel – right of image) in a case of vasculitis (eosinophilic granulomatosis with polyangiitis).

Nomenclature

A misnomer

It is to be noted that the term fibrinoid necrosis is, in fact, considered a misnomer, as the intense eosinophilic staining of the accumulated plasma proteins masks the true nature of the underlying changes in the blood vessel, and makes it virtually impossible to definitively determine whether the cells of the vessel wall are actually undergoing necrosis.

A 2000 review stated that "whether the lesion is truly necrotic, in the sense that it reflects the result of unprogrammed cell death, has never been investigated in depth", and an electron microscopy study examining fibrinoid necrosis in rat models with induced pulmonary hypertension found that fibrinoid changes weren't necessarily associated with necrosis of the smooth muscles of the media, and therefore recommended using the term fibrinoid vasculosis instead.

However, despite the inaccuracy, the microscopic characteristics of fibrinoid changes strongly resemble those of necrotic tissue, which is why the term fibrinoid necrosis continues to be used, even though it may not fully reflect the true underlying process.

Fibrinoid necrosis and lipohyalinosis

In 1971, CM Fisher, a pioneering figure in cerebral vascular diseases, proposed using the term lipohyalinosis as a replacement for fibrinoid necrosis, based on his observation that the affected fibrinoid areas also contained lipid.

The term lipohyalinosis was intended to serve as a synonym for fibrinoid necrosis, yet it is strictly used to describe the pathological fibrinoid changes in the cerebral vessels of patients with malignant hypertension. Even though the same pathological process, that affects cerebral blood vessels in malignant hypertension, also occurs in the arterioles of other organs, such as the kidneys and mesentery, lipohyalinosis is not used to describe these changes outside the brain, and fibrinoid necrosis remains the more widely recognized term for similar processes in other organs.

However, a common misconception in many textbooks is the failure to clarify that lipohyalinosis and fibrinoid necrosis are actually two descriptions of the same pathological process.

Instead of recognizing their equivalence, they are often presented as distinct stages, where lipohyalinosis is mistakenly described as a later consequence of fibrinoid necrosis, or lipohyalinosis is sometimes erroneously used interchangeably with arteriolosclerosis, which is a much broader term used to describe pathological changes in small arteries caused by a variety of conditions. Mislabeling lipohyalinosis as arteriolosclerosis overlooks the specific nature of lipohyalinosis as a condition involving fibrinoid necrosis (a particular form of vascular injury) and contributes to confusion.

Localization

Fibrinoid necrosis predominantly affects small blood vessels, such as arterioles and glomeruli, but it can also involve medium-sized vessels, as observed in conditions like polyarteritis nodosa. It can also exhibit a highly segmental distribution, where the fibrinoid material does not uniformly coat the affected vessel but instead appears in isolated patches that are spaced along the length of the vessel wall.

Fibrinoid infiltration in affected vessels may be confined to the subintimal region, as the ground substance of the intima and the inner elastic lamina often act as a barrier, limiting further penetration of fibrin into the arterial wall. However, if the internal elastic lamina is disrupted, fibrin may extend into the media, where it is typically contained by the outer elastic lamina, potentially spreading circumferentially along its inner surface. In some cases, fibrin may extend into the adventitia or even escape from the vessels into surrounding perivascular tissue or adjacent spaces. This phenomenon is observed in conditions such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, where fibrin can infiltrate the urinary space near glomerular capillaries or the air space adjacent to alveolar capillaries.

Associated diseases

Fibrinoid necrosis is observed in a wide range of pathological conditions such as:

• Immunologically-mediated vasculitides including:

1. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis: Fibrinoid necrosis is a classical finding in these small-vessel vasculitides, and it has been referred to as the "the ANCA-associated lesion" even though it occurs in other conditions as well.
2. Polyarteritis nodosa (PAN): The hallmark morphological characteristic of PAN is fibrinoid necrosis. In contrast, fibrinoid necrosis in Kawasaki disease is less pronounced than in PAN, despite both being forms of medium-sized vessel vasculitides.
3. Systemic lupus erythematosus.
4. Leucocytoclastic vasculitis.
5. Systemic sclerosis, arthus reaction (a type III hypersensitivity reaction) and rheumatoid subcutaneous nodules.

• Malignant hypertension: Fibrinoid necrosis arises in the systemic circulation as a typical feature of malignant hypertension, and it's observed, for example, in the arterioles of the kidney, brain, retina, and other organs.
• Thrombotic microangiopathy, and rejection of kidney grafts.
• Preeclampsia: Fibrinoid necrosis occurs in the uterine spiral arterioles in preeclampsia, and involves the deposition of a dense, eosinophilic material beneath the endothelial lining of the affected vessels.
• Gestational diabetes mellitus may also result in fibrinoid necrosis, and vascular lesions similar to preeclampsia.
• Cerebral amyloid angiopathy.
• COVID-19 infection.
• Sarcoidosis: Fibrinoid necrosis may be observed in the central region of sarcoid granulomas, providing a histopathological distinction from the [[caseous necro