Fibrinoid necrosis

Last updated

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. [1] [2] [3] [4]

Contents

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. [4] [5] [6] [7]

The earliest documented identification of fibrinoid 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. [8] [9]

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. [4] [8] 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. [4]

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. [8]

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. Fibrinoid necrosis.jpg
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). Churg-Strauss syndrome - high mag.jpg
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

The term fibrinoid necrosis is, in fact, considered a misnomer, [1] [10] 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. [1] [11]

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", [8] 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. [6]

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. [10]

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. [4]

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. [4]

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. [12]

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. [12]

Localization

Fibrinoid necrosis predominantly affects small blood vessels, such as arterioles and glomeruli, [3] but it can also involve medium-sized vessels, as observed in conditions like polyarteritis nodosa. [13] 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. [4] [14]

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. [6] 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. [6] [15] 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. [16]

Associated diseases

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

  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 ANCA-associated lesion" even though it occurs in other conditions as well. [8]
  2. Polyarteritis nodosa (PAN): The hallmark morphological characteristic of PAN is fibrinoid necrosis. [1] In contrast, fibrinoid necrosis in Kawasaki disease is less pronounced than in PAN, despite both being forms of medium-sized vessel vasculitides. [17]
  3. Systemic lupus erythematosus. [14]
  4. Leucocytoclastic vasculitis. [18]
  5. Systemic sclerosis, arthus reaction (a type III hypersensitivity reaction) and rheumatoid subcutaneous nodules. [17]
An H&E-stained micrograph of a rheumatoid nodule reveals its characteristic histological structure, featuring a central core composed of fibrinoid necrosis, and surrounding this core is a layer of palisading macrophages and epithelioid histiocytes. Histopathology of a rheumatoid nodule.png
An H&E-stained micrograph of a rheumatoid nodule reveals its characteristic histological structure, featuring a central core composed of fibrinoid necrosis, and surrounding this core is a layer of palisading macrophages and epithelioid histiocytes.

Pathogenesis

Fibrinoid necrosis occurs as a consequence of endothelial injury, which permits the leakage of plasma proteins into the blood vessel walls. [2] [3] [28] This endothelial damage may arise due to a variety of underlying factors; for instance:

Endothelial cell damage results in the loss of the normal barrier function, and allows plasma components, including coagulation factors, to escape from the bloodstream and leak out into the blood vessel walls and the surrounding spaces. The coagulation factors that leak from the damaged blood vessels interact with various thrombogenic substances, such as tissue factor, which culminates in the formation of fibrin, whose accumulation leads to the characteristic appearance of fibrinoid necrosis. [5] [33]

Clinical relevance

Pathological consequences

Ischemia

Hemorrhage

Whenever hypertension induces fibrinoid necrosis in the small cerebral arteries, this considerably raises the risk of intracerebral hemorrhage (ICH) due to two main factors: [31]

  1. The deposition of fibrinoid material in the vessel wall leads to thickening of the arterial walls, making them progressively more rigid and less elastic.
  2. The narrowing of the arterial lumens further exacerbates this by raising intraluminal pressure.

As a result, the small cerebral arteries become more fragile and prone to rupture, which may ultimately lead to ICH.

Retinal detachment

When blood pressure rises significantly, as in malignant hypertension or eclampsia, retinal arterioles can undergo fibrinoid necrosis, reducing blood supply to the choriocapillaris, which is responsible for nourishing the retinal pigment epithelium (RPE). Ischemia disrupts RPE function, compromises the blood-retinal barrier and causes fluid leakage into the subretinal space, and the development of exudative retinal detachment. [35] [36]

Diagnostic value

Fibrinoid necrosis serves as an important diagnostic clue in recognizing vascular pathologies, and helping to guide further investigation and treatment; for instance:

  1. Neutrophilic infiltration in and around the vessel wall with leukocytoclasia.
  2. Fibrinoid necrosis.
  3. Vessel wall and tissue damage.

The lack of fibrinoid necrosis and inflammatory infiltration in the vessel may preclude the diagnosis of classic LCV, and necessitates further evaluation. [40] However, it is to be noted that these histological features tend to progress gradually over time, and a biopsy taken too early or too late might miss the "textbook" full-blown changes of LCV. [39]

Prognostic value

Fibrinoid necrosis is included in the modified National Institutes of Health (NIH) activity index for lupus nephritis (LN), which is a scoring system used to assess the severity of LN based on histopathologic findings from kidney biopsies. [14]

The activity index is based on the evaluation of six histologic features that indicate active inflammation, each of which is assigned a score from 0-3 depending on the degree of glomerular involvement. [14] [41] The score of fibrinoid necrosis and cellular/fibrocellular crescents is multiplied by two, because these two lesions were considered to be associated with a higher level of severity; [42] this gives the activity index a total score of 0-24. [note 2]

The activity index correlates with the level of active inflammation in LN, [41] and serves as a general framework for guiding treatment decisions; the higher the NIH activity score, the more intensive the immunosuppressive treatment required. [43]

Notes

  1. ↑ This figure illustrates that Masson's trichrome stain also helps to distinguish between fibrinoid necrosis, and sclerosis in renal biopsies.
  2. ↑ This figure illustrates the modified NIH activity and chronicity indices for lupus nephritis.

Related Research Articles

<span class="mw-page-title-main">Blood vessel</span> Tubular structure carrying blood

Blood vessels are the tubular structures of a circulatory system that transport blood throughout a vertebrate's body. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste and carbon dioxide away from the tissues. Some tissues such as cartilage, epithelium, and the lens and cornea of the eye are not supplied with blood vessels and are termed avascular.

<span class="mw-page-title-main">Capillary</span> Smallest type of blood vessel

A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the site of the exchange of many substances from the surrounding interstitial fluid, and they convey blood from the smallest branches of the arteries (arterioles) to those of the veins (venules). Other substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in microcirculation.

<span class="mw-page-title-main">Thrombus</span> Blood clot

A thrombus, colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through a healthy blood vessel in the circulatory system.

<span class="mw-page-title-main">Microangiopathy</span> Medical condition

Microangiopathy is a disease of the microvessels, small blood vessels in the microcirculation. It can be contrasted to macroangiopathies such as atherosclerosis, where large and medium-sized arteries are primarily affected.

<span class="mw-page-title-main">Arteriole</span> Small arteries in the microcirculation

An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries.

<span class="mw-page-title-main">Vasculitis</span> Medical disorders that destroy blood vessels by inflammation

Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities.

<span class="mw-page-title-main">Endothelial dysfunction</span> Impaired function of the inner lining of blood/lymph vessels

In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. The main cause of endothelial dysfunction is impaired bioavailability of nitric oxide.

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">Hypertensive kidney disease</span> Medical condition

Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis. It should be distinguished from renovascular hypertension, which is a form of secondary hypertension, and thus has opposite direction of causation.

Microscopic polyangiitis is an autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of granulomatous inflammation.

<span class="mw-page-title-main">Hypertensive emergency</span> Very high blood pressure and signs of organ damage

A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems. It is different from a hypertensive urgency by this additional evidence for impending irreversible hypertension-mediated organ damage (HMOD). Blood pressure is often above 200/120 mmHg, however there are no universally accepted cutoff values.

<span class="mw-page-title-main">Intraparenchymal hemorrhage</span> Bleeding within parenchymal tissue of the brain

Intraparenchymal hemorrhage is one form of intracerebral bleeding in which there is bleeding within brain parenchyma. The other form is intraventricular hemorrhage).

<span class="mw-page-title-main">Arteriolosclerosis</span> Hardening of small arteries (arterioles)

Arteriolosclerosis is a form of cardiovascular disease involving hardening and loss of elasticity of arterioles or small arteries and is most often associated with hypertension and diabetes mellitus. Types include hyaline arteriolosclerosis and hyperplastic arteriolosclerosis, both involved with vessel wall thickening and luminal narrowing that may cause downstream ischemic injury. The following two terms whilst similar, are distinct in both spelling and meaning and may easily be confused with arteriolosclerosis.

Hypertensive encephalopathy (HE) is general brain dysfunction due to significantly high blood pressure. Symptoms may include headache, vomiting, trouble with balance, and confusion. Onset is generally sudden. Complications can include seizures, posterior reversible encephalopathy syndrome, and bleeding in the back of the eye.

Lipohyalinosis is a cerebral small vessel disease affecting the small arteries, arterioles or capillaries in the brain. Originally defined by C. Miller Fisher as 'segmental arteriolar wall disorganisation', it is characterized by vessel wall thickening and a resultant reduction in luminal diameter. Fisher considered this small vessel disease to be the result of hypertension, induced in the acute stage by fibrinoid necrosis that would lead to occlusion and hence lacunar stroke. However, recent evidence suggests that endothelial dysfunction as a result of inflammation is a more likely cause for it. This may occur subsequent to blood–brain barrier failure, and lead to extravasation of serum components into the brain that are potentially toxic. Lacunar infarction could thus occur in this way, and the narrowing – the hallmark feature of lipohyalinosis – may merely be a feature of the swelling occurring around it that squeezes on the structure.

<span class="mw-page-title-main">Systemic vasculitis</span> Medical condition

Necrotizing vasculitis, also called systemic necrotizing vasculitis, is a general term for the inflammation of veins and arteries that develops into necrosis and narrows the vessels.

Diffuse proliferative glomerulonephritis (DPGN) is a type of glomerulonephritis that is the most serious form of renal lesions in SLE and is also the most common, occurring in 35% to 60% of patients. In absence of SLE, DPGN pathology looks more like Membranoproliferative glomerulonephritis

<span class="mw-page-title-main">Livedoid vasculopathy</span> Blood vessel disorder causing ulcers in the lower limbs

Livedoid vasculopathy (LV) is an uncommon thrombotic dermal vasculopathy that is characterized by excruciating, recurrent ulcers on the lower limbs. Livedo racemosa, along with painful ulceration in the distal regions of the lower extremities, is the characteristic clinical appearance. It heals to form porcelain-white, atrophic scars, also known as Atrophie blanche.

<span class="mw-page-title-main">Lupus vasculitis</span> Medical condition

Lupus vasculitis is one of the secondary vasculitides that occurs in approximately 50% of patients with systemic lupus erythematosus (SLE).

<span class="mw-page-title-main">J. Charles Jennette</span> Doctor, academic, and author

J. Charles Jennette is a physician, nephropathologist, academic, and author. He served as Kenneth M. Brinkhous Distinguished Professor and Chair of Pathology and Laboratory Medicine at the University of North Carolina at Chapel Hill School of Medicine, and Chief of Pathology and Laboratory Medicine Services at UNC Hospitals from 1999 to 2019.

References

  1. 1 2 3 4 5 Strayer, DS; Rubin, E; Saffitz, JE; Schiller, AL (2015). Rubin's Pathology: Clinicopathologic Foundations of Medicine (7th ed.). Philadelphia, Penn.: Wolters Kluwer. ISBN   978-1-4511-8390-0.
  2. 1 2 Miller, MA; Zachary, JF (2017). "Mechanisms and Morphology of Cellular Injury, Adaptation, and Death". Pathologic Basis of Veterinary Disease: 2–43.e19. doi:10.1016/B978-0-323-35775-3.00001-1. ISBN   978-0-323-35775-3. PMC   7171462 .
  3. 1 2 3 Chen, H; Liu, Y; Wei, L; Wang, H; Zheng, Z; Yan, T; Jia, J; Li, D (11 December 2023). "The effect of fibrinoid necrosis on the clinical features and outcomes of primary IgA nephropathy". BMC Nephrology. 24 (1): 366. doi: 10.1186/s12882-023-03419-4 . PMC   10712095 . PMID   38082385.
  4. 1 2 3 4 5 6 7 8 Rosenblum, WI (October 2008). "Fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal". Acta Neuropathologica. 116 (4): 361–9. doi:10.1007/s00401-008-0416-9. PMID   18642006.
  5. 1 2 Hano, H; Takagi, I; Nagatsuma, K; Lu, T; Meng, C; Chiba, S (28 January 2007). "An autopsy case showing massive fibrinoid necrosis of the portal tracts of the liver with cholangiographic findings similar to those of primary sclerosing cholangitis". World Journal of Gastroenterology. 13 (4): 639–42. doi: 10.3748/wjg.v13.i4.639 (inactive 2024-11-26). PMC   4065992 . PMID   17278236.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  6. 1 2 3 4 5 Heath, D; Smith, P (October 1978). "The electron microscopy of "fibrinoid necrosis" in pulmonary arteries". Thorax. 33 (5): 579–95. doi:10.1136/thx.33.5.579. PMC   470940 . PMID   31704.
  7. ↑ WIENER, J; SPIRO, D; LATTES, RG (September 1965). "The Cellular Pathology of Experimental Hypertension. II. Arteriolar Hyalinosis and Fibrinoid Change". The American Journal of Pathology. 47 (3): 457–85. PMC   1920447 . PMID   14334752.
  8. 1 2 3 4 5 Bajema, IM; Bruijn, JA (July 2000). "What stuff is this! A historical perspective on fibrinoid necrosis". The Journal of Pathology. 191 (3): 235–8. doi: 10.1002/(SICI)1096-9896(0000)9999:9999<N/A::AID-PATH610>3.0.CO;2-I . PMID   10878543.
  9. ↑ Scott, GB (June 1968). "Trypan blue and the generalized Shwartzman reaction. The nature and formation of fibrinoid material in the pulmonary arteries". British Journal of Experimental Pathology. 49 (3): 251–6. PMC   2093816 . PMID   5665438.
  10. 1 2 Cross, Simon S. (2013). Underwood's Pathology: A Clinical Approach (6th ed.). Churchill Livingstone. ISBN   978-0-7020-4672-8.
  11. ↑ Jennette, JC; Falk, RJ; Hu, P; Xiao, H (24 January 2013). "Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis". Annual Review of Pathology. 8: 139–60. doi:10.1146/annurev-pathol-011811-132453. PMC   5507606 . PMID   23347350.
  12. 1 2 Rosenblum, William I (10 September 2021). "Lipohyalinosis and Fibrinoid: Consistent and Important Failure to Understand These Are Synonyms". Journal of Neuropathology & Experimental Neurology. 80 (8): 802–803. doi: 10.1093/jnen/nlab009 . PMID   33684938.
  13. ↑ Aw, DKL; Vijaykumar, K; Cheng, SC; Tang, TY; Tay, JS; Choke, ETC (December 2023). "A case of severe polyarteritis nodosa with critical limb threatening ischemia-promising treatment with sirolimus drug-coated angioplasty". Journal of Vascular Surgery Cases and Innovative Techniques. 9 (4): 101266. doi:10.1016/j.jvscit.2023.101266. PMC   10725072 . PMID   38106351.
  14. 1 2 3 4 Bajema, IM; Wilhelmus, S; Alpers, CE; Bruijn, JA; Colvin, RB; Cook, HT; D'Agati, VD; Ferrario, F; Haas, M; Jennette, JC; Joh, K; Nast, CC; Noël, LH; Rijnink, EC; Roberts, ISD; Seshan, SV; Sethi, S; Fogo, AB (April 2018). "Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices". Kidney International. 93 (4): 789–796. doi: 10.1016/j.kint.2017.11.023 . hdl: 10044/1/57351 . PMID   29459092.
  15. ↑ Cassisa, A; Cima, L (April 2024). "Cutaneous vasculitis: insights into pathogenesis and histopathological features". Pathologica. 116 (2): 119–133. doi:10.32074/1591-951X-985. PMC   11138767 . PMID   38767544.
  16. ↑ Sinico, RA; Guillevin, L (2020). Anti-Neutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis. Springer Nature. doi:10.1007/978-3-030-02239-6. ISBN   978-3-030-02238-9.
  17. 1 2 3 4 Kumar, Vinay; Abbas, Abul K.; Aster, Jon C. (24 June 2014). Robbins & Cotran Pathologic Basis of Disease (9th ed.). Elsevier Health Sciences. ISBN   978-0-323-29635-9.
  18. 1 2 Baigrie, D; Crane, JS (January 2024), "Leukocytoclastic Vasculitis.", StatPearls, Treasure Island, Florida (FL): StatPearls Publishing, PMID   29489227
  19. ↑ Naranjo, M; Chauhan, S; Paul, M (January 2024), "Malignant Hypertension.", StatPearls, Treasure Island, Florida (FL): StatPearls Publishing, PMID   29939523
  20. 1 2 Kasper, Dennis L.; Fauci, Anthony S.; Hauser, Stephen L.; Longo, Dan L.; Jameson, J. Larry; Loscalzo, Joseph (6 February 2018). Harrison's Principles of Internal Medicine 20/E (Vol.1 & Vol.2) (ebook) (20th ed.). McGraw Hill Professional. ISBN   978-1-259-64404-7.
  21. ↑ Gusella, A; Martignoni, G; Giacometti, C (18 July 2024). "Behind the Curtain of Abnormal Placentation in Pre-Eclampsia: From Molecular Mechanisms to Histological Hallmarks". International Journal of Molecular Sciences. 25 (14): 7886. doi: 10.3390/ijms25147886 . PMC   11277090 . PMID   39063129.
  22. ↑ Basri, NI; Murthi, P; Abd Rahman, R (6 September 2024). "Hydroxychloroquine as an Adjunct Therapy for Diabetes in Pregnancy". International Journal of Molecular Sciences. 25 (17): 9681. doi: 10.3390/ijms25179681 . PMC   11395545 . PMID   39273629.
  23. ↑ Agarwal, A; Ajmera, P; Sharma, P; Kanekar, S (April 2024). "Cerebral microbleeds: Causes, clinical relevance, and imaging approach - A narrative review". Journal of Neurosciences in Rural Practice. 15 (2): 169–181. doi:10.25259/JNRP_351_2023. PMC   11090589 . PMID   38746527.
  24. ↑ Gopallawa, I; Dehinwal, R; Bhatia, V; Gujar, V; Chirmule, N (2023). "A four-part guide to lung immunology: Invasion, inflammation, immunity, and intervention". Frontiers in Immunology. 14: 1119564. doi: 10.3389/fimmu.2023.1119564 . PMC   10102582 . PMID   37063828.
  25. ↑ Septimiu-Radu, S; Gadela, T; Gabriela, D; Oancea, C; Rosca, O; Lazureanu, VE; Fericean, RM; Bratosin, F; Dumitrescu, A; Stoicescu, ER; Bagiu, I; Murariu, M; Mavrea, A (6 March 2023). "A Systematic Review of Lung Autopsy Findings in Elderly Patients after SARS-CoV-2 Infection". Journal of Clinical Medicine. 12 (5): 2070. doi: 10.3390/jcm12052070 . PMC   10004532 . PMID   36902856.
  26. ↑ Weeratunga, P; Moller, DR; Ho, LP (2 January 2024). "Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis". The Journal of Clinical Investigation. 134 (1). doi:10.1172/JCI175264. PMC   10760966 . PMID   38165044.
  27. ↑ Scheepens, JCC; Taphoorn, MJB; Koekkoek, JAF (1 November 2024). "Patient-reported outcomes in neuro-oncology". Current Opinion in Oncology. 36 (6): 560–568. doi:10.1097/CCO.0000000000001078. PMC   11460742 . PMID   38984633.
  28. ↑ Adigun, R; Basit, H; Murray, J (January 2024), "Cell Liquefactive Necrosis.", StatPearls, Treasure Island, Florida (FL): StatPearls Publishing, PMID   28613685
  29. ↑ Gluhovschi, C; Gadalean, F; Velciov, S; Nistor, M; Petrica, L (6 November 2023). "Three Diseases Mediated by Different Immunopathologic Mechanisms-ANCA-Associated Vasculitis, Anti-Glomerular Basement Membrane Disease, and Immune Complex-Mediated Glomerulonephritis-A Common Clinical and Histopathologic Picture: Rapidly Progressive Crescentic Glomerulonephritis". Biomedicines. 11 (11): 2978. doi: 10.3390/biomedicines11112978 . PMC   10669599 . PMID   38001978.
  30. 1 2 Mohan, Harsh (31 October 2014). Textbook of Pathology (7th ed.). Jaypee Brothers Medical Publishers Pvt. Limited. ISBN   978-93-5152-369-7.
  31. 1 2 Huang, B; Chen, A; Sun, Y; He, Q (19 June 2024). "The Role of Aging in Intracerebral Hemorrhage". Brain Sciences. 14 (6): 613. doi: 10.3390/brainsci14060613 . PMC   11201415 . PMID   38928613.
  32. ↑ Romano, A; Moltoni, G; Blandino, A; Palizzi, S; Romano, A; de Rosa, G; De Blasi Palma, L; Monopoli, C; Guarnera, A; Minniti, G; Bozzao, A (21 October 2023). "Radiosurgery for Brain Metastases: Challenges in Imaging Interpretation after Treatment". Cancers. 15 (20): 5092. doi: 10.3390/cancers15205092 . PMC   10605307 . PMID   37894459.
  33. ↑ Jennette, JC; Falk, RJ (August 2014). "Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease". Nature Reviews. Rheumatology. 10 (8): 463–73. doi: 10.1038/nrrheum.2014.103 . PMID   25003769.
  34. ↑ Marcinkowska, W; Zielinska, N; Szewczyk, B; Łabętowicz, P; Głowacka, M; Olewnik, Ł (11 October 2024). "Morphological Variability of the Sural Nerve and Its Clinical Significance". Journal of Clinical Medicine. 13 (20): 6055. doi: 10.3390/jcm13206055 . PMC   11508416 . PMID   39458004.
  35. ↑ Mishra, P; Kanaujia, V; Kesarwani, D; Sharma, K; Nanda, J; Mishra, P (June 2024). "Visual Outcomes in Malignant Hypertensive Retinopathy Cases: A Clinical and Spectral Domain Optical Coherence Tomography Study". Cureus. 16 (6): e62945. doi: 10.7759/cureus.62945 . PMC   11265969 . PMID   39050341.
  36. ↑ Hayreh, SS; Hayreh, SB (September 2023). "Uveal vascular bed in health and disease: lesions produced by occlusion of the uveal vascular bed and acute uveal ischaemic lesions seen clinically. Paper 2 of 2". Eye. 37 (13): 2617–2648. doi:10.1038/s41433-023-02417-y. PMC   10482881 . PMID   37185956.
  37. ↑ Monti, S; Schäfer, VS; Muratore, F; Salvarani, C; Montecucco, C; Luqmani, R (2023). "Updates on the diagnosis and monitoring of giant cell arteritis". Frontiers in Medicine. 10: 1125141. doi: 10.3389/fmed.2023.1125141 . hdl: 11380/1299527 . PMC   9995793 . PMID   36910481.
  38. ↑ Matsuo, T; Hiramatsu-Asano, S; Sawachika, H; Nishimura, H (June 2023). "ANCA-associated vasculitis with scleritis, corneal melt, and perforation rescued by rituximab: Case report and literature review". Clinical Case Reports. 11 (6): e7595. doi:10.1002/ccr3.7595. PMC   10282114 . PMID   37351359.
  39. 1 2 Fraticelli, P; Benfaremo, D; Gabrielli, A (June 2021). "Diagnosis and management of leukocytoclastic vasculitis". Internal and Emergency Medicine. 16 (4): 831–841. doi:10.1007/s11739-021-02688-x. PMC   8195763 . PMID   33713282.
  40. ↑ Oprinca, GC; Mohor, CI; Oprinca-Muja, A; Hașegan, A; Cristian, AN; Fleacă, SR; Boeraș, I; Cardoș, R; Atasie, D; Mihalache, M; Mihalache, C; Tâlvan, ET; Mohor, CI (24 February 2024). "Unveiling the Pathological Mechanisms of Death Induced by SARS-CoV-2 Viral Pneumonia". Microorganisms. 12 (3): 459. doi: 10.3390/microorganisms12030459 . PMC   10972137 . PMID   38543510.
  41. 1 2 Mina, R; Abulaban, K; Klein-Gitelman, MS; Eberhard, BA; Ardoin, SP; Singer, N; Onel, K; Tucker, L; O'neil, K; Wright, T; Brooks, E; Rouster-Stevens, K; Jung, L; Imundo, L; Rovin, B; Witte, D; Ying, J; Brunner, HI (February 2016). "Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus". Arthritis Care & Research. 68 (2): 195–202. doi:10.1002/acr.22651. PMC   4720587 . PMID   26213987.
  42. ↑ Choi, SE; Fogo, AB; Lim, BJ (March 2023). "Histologic evaluation of activity and chronicity of lupus nephritis and its clinical significance". Kidney Research and Clinical Practice. 42 (2): 166–173. doi:10.23876/j.krcp.22.083. PMC   10085727 . PMID   37037479.
  43. ↑ Fava, A; Buyon, J; Magder, L; Hodgin, J; Rosenberg, A; Demeke, DS; Rao, DA; Arazi, A; Celia, AI; Putterman, C; Anolik, JH; Barnas, J; Dall'Era, M; Wofsy, D; Furie, R; Kamen, D; Kalunian, K; James, JA; Guthridge, J; Atta, MG; Monroy Trujillo, J; Fine, D; Clancy, R; Belmont, HM; Izmirly, P; Apruzzese, W; Goldman, D; Berthier, CC; Hoover, P; Hacohen, N; Raychaudhuri, S; Davidson, A; Diamond, B; Accelerating Medicines Partnership in RA/SLE, network; Petri, M (23 January 2024). "Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis". JCI Insight. 9 (2). doi:10.1172/jci.insight.172569. PMC   10906224 . PMID   38258904.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.