The document discusses systemic lupus erythematosus (SLE) and its effects on the kidneys, known as lupus nephritis. It defines SLE as an autoimmune disease that causes organ and tissue damage mediated by autoantibodies and immune complexes. Around 90% of SLE patients are women of childbearing age. The document outlines the classification criteria for diagnosing SLE and describes the clinical manifestations and role of renal biopsy in diagnosing lupus nephritis. It discusses the pathologic findings of lupus nephritis under light microscopy, immunofluorescence, and electron microscopy and provides the 2003 classification system for lupus nephritis.
Cirrhosis is a diffuse process characterized by liver necrosis & fibrosis and conversion of normal liver architecture into structurally abnormal nodules that lack normal lobular organization
Please find the power point on Oesopaheal Varices. I tried present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
A presentation on the pathology and current management (with Especial emphasis on surgical management) of Portal Hypertension; a common complication of liver cirrhosis among other liver diseases. Being a copy of seminar presentation I for the HepatoPancreaticoBiliary Unit of the Division of General Surgery, Ahmadu Belllo University Teaching Hospital, Zaria.
Cirrhosis is a diffuse process characterized by liver necrosis & fibrosis and conversion of normal liver architecture into structurally abnormal nodules that lack normal lobular organization
Please find the power point on Oesopaheal Varices. I tried present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
A presentation on the pathology and current management (with Especial emphasis on surgical management) of Portal Hypertension; a common complication of liver cirrhosis among other liver diseases. Being a copy of seminar presentation I for the HepatoPancreaticoBiliary Unit of the Division of General Surgery, Ahmadu Belllo University Teaching Hospital, Zaria.
most of the glomerular diseases , either primary or secondary..touching all the aspects including light microscopy, electron microscopy and immunoflourescence.
to download this presentation from this link
https://mohmmed-ink.blogspot.com/2020/12/obesity.html
obesity, causes, diagnosis, complications, treatment, prevention.
The non-Hodgkin lymphomas include a diverse and complex group of malignancies of lymphoreticular histogenesis and differentiation.
In most instances, they initially arise within lymph nodes and tend to grow as solid masses.
The non-Hodgkin lymphomas most commonly originate from cells of the B-lymphocyte series, with an estimated 85% of European and American lymphoid neoplasms having this derivation.
Tumors with a T-lymphocyte derivation are less common, whereas true histiocyte-derived lymphomas are even rarer.
Genetic abnormalities like nonrandom chromosomal and molecular rearrangements play an important role in the pathogenesis of many lymphomas and correlate with histology and immunophenotype.
Most lymphomas do not have a familial pattern; however, coexistence of multiple breast cancers, ovarian cancer, sarcomas, and lymphomas in a family may suggest an inherited abnormality in tumor suppressor genes.
Environmental factors also seem to play a role in the development of NHL. Certain chemicals have been linked to the development of NHL include a variety of pesticides and herbicides (e.g. organophosphates, chlorophenols), solvents and organic chemicals (e.g. benzene, carbon tetrachloride), and wood preservatives.
Thus certain workers like pesticide applicators, workers in the petroleum, rubber, plastics, and synthetic industries have a slightly increased risk of NHL.
Patients who receive cancer chemotherapy and/or radiation therapy are at increased risk of developing NHL.
Several viruses have been implicated in the pathogenesis of NHL, including the Epstein-Barr virus in Burkitt’s lymphoma (especially in endemic areas of Africa), sinonasal lymphoma in Asia and South America, and lymphomas in immunocompromised patients; HTLV-1 Human T-lymphotropic Virus in adult T-cell lymphoma/leukemia; and human herpesvirus 8 (HHV 8) in body cavity-based lymphomas in patients with HIV infection.
Immunodeficiency states that seem to predispose to NHL include congenital immunodeficiency states (e.g. ataxia telangiectasia, Wiskott–Aldrich syndrome, common variable hypogammaglobulinemia, severe combined immunodeficiency (SCID) as well as acquired immunodeficiency states (e.g. HIV infection, iatrogenic immunosuppression for solid organ or bone marrow transplant recipients).
Connective-tissue disorders, including Sjögren syndrome, rheumatoid arthritis, chronic lymphocytic thyroiditis, and systemic lupus erythematosus (SLE) are also associated with increased risk of NHL.
The microscopic appearance of the lesional cells was used in the past to classify the tumors as either lymphocytic or histiocytic.
With the development of modern immunologic techniques, however, it is now known that many of the lesions that had been classified as histiocytic were in fact neoplasms composed of transformed B lymphocytes. In the early 1980s, a group of American pathologists devised a classification scheme, known as the Working Formulation for Clinical Use.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
1. SLE & KIDNEY
Ayan Santra,
PGT, Dept. of Pathology
Burdwan Medical College
2. Definition
• Systemic lupus erythematosus (SLE) is an
• autoimmune disease in which organs,
tissues, and cells undergo damage mediated by
tissue-binding autoantibodies and immune
complexes.
• Ninety percent of patients are women of child-
bearing years;
• people of both genders, all ages, and all ethnic
groups are susceptible.
3. Classification Criteria for the
Diagnosis of SLE(≥4 criteria at any
point)
• Malar rash Fixed erythema, flat or raised, over the malar eminences
• Discoid rash Erythematous circular raised patches with adherent
keratotic scaling and follicular plugging; atrophic scarring may occur
• Photosensitivity Exposure to ultraviolet light causes rash
• Oral ulcers Includes oral and nasopharyngeal ulcers, observed by
physician
• Arthritis Nonerosive arthritis of two or more peripheral joints, with
tenderness, swelling, or effusion
• Serositis Pleuritis or pericarditis documented by ECG or rub or
evidence of effusion
4. Classification Criteria for the
Diagnosis of SLE(≥4 criteria at any
point)
• Renal disorder Proteinuria 0.5 g/d or ≥3+, or cellular casts
• Neurologic disorder Seizures or psychosis without other
causes
• Hematologic disorder Hemolytic anemia or leukopenia
(<4000/L) or lymphopenia (<1500/L) or thrombocytopenia
(<100,000/L) in the absence of offending drugs
• Immunologic disorder Anti-dsDNA, anti-Sm, and/or
antiphospholipid
• Antinuclear antibodies An abnormal titer of ANA by
immunofluorescence or an equivalent assay at any point in
time in the absence of drugs known to induce ANAs
5. Lupus Nephritis
• The renal manifestations of SLE is called lupus
nephritis.
• Clinical or morphologic involvement of the
kidney in SLE occurs in 50% to 80% of lupus
patients at any moment during the course of
their disease.
• Renal alterations are found in almost 90% of
lupus patients at autopsy
6. Clinical manifestations
• Onset of renal involvement is most common
within the first year
• Manifestations varies according to stage of
disease
• From asymptomatic to renal failure
• The nephritis has the ability to transform from
one morphologic pattern to another
spontaneously or after treatment
7. • In class I and II (mesangial) lupus nephritis,
microscopic hematuria is the leading
symptom. Proteinuria may be present, but it is
not severe or in the nephrotic range.
• In classes III and IV (proliferative) lupus
nephritis, nephritic syndrome, with or
without nephrotic-range proteinuria, and
frequently low complement levels are seen.
• In class V (membranous) lupus nephritis,
severe, usually nephrotic-range proteinuria
is the most significant symptom, with
microscopic hematuria.
• Class VI (chronic sclerosing) lupus nephritis is
characterized by chronic renal failure.
8. Role of Renal Biopsy
• It is instrumental in establishing a diagnosis of
SLE or lupus nephritis.
• Indications are:
• newly diagnosed SLE,
• newly appearing renal symptoms;
• follow up every 6 months or more after therapy
to gauge the efficacy of treatment and guide
further therapeutic management;
• sudden change in renal symptoms & findings
9. • The biopsy should contain a minimum of 10
glomeruli for light microscopy analysis
• H&E, methenamine-silver, trichrome, and PAS
• Immunofluorescence (IF) should include
staining for IgG, IgA, IgM, C3 and C1q
• It is possible to do an adequate and complete
classification of the lupus nephritis, without
electron microscopy (EM); In cases without IF,
EM is essential
10. Terminologies
• Focal-Involving <50% of glomeruli
• Diffuse-Involving 50% or more of glomeruli
• Segmental-Involving part of a glomerular tuft(<50%)
• Global-Involving all of a glomerular tuft(>50%)
• Karyorrhexis: presence of pyknotic and fragmented
nuclei
• Mesangial hypercellularity- three or more mesangial
cells in mesangial areas away from the vascular pole,
assessed in 3-micron-thick histologic sections
11. Terminologies
• Endocapillary hypercellularity- Increased cellularity
internal to the GBM composed of leukocytes, endothelial
cells and/or mesangial cells
• Extracapillary hypercellularity- Increased cellularity in
Bowman’s space, i.e. > one layer of parietal or visceral
epithelial cells, or monocytes/macrophages
• Fibrinoid necrosis- Lytic destruction of cells and matrix
with deposition of acidophilic fibrin-rich material
• Sclerosis- Increased collagenous extracellular matrix
that is expanding the mesangium, obliterating capillary
lumens or forming adhesions to Bowman’s capsule
• Hyaline-Glassy acidophilic extracellular material
14. Pathologic Findings
• Gross Pathology:
• Acute disease: enlarged, swollen kidneys with
petechial hemorrhages and focal, shallow,
superficial scars.
• With immunosuppressive therapy: a
combination of chronic and acute changes, with
a contracted or swollen appearance.
15. Light Microscopy
• Glomeruli:
• 1. Immune deposits: large and wide spread
• Hyaline and hyper eosinophilic in H&E stain
• The trichrome stain highlights the deposits as red
(or fuchsinophilic) against the blue-staining
glomerular matrix components
• When large enough to completely involve the
peripheral circumference of the glomerular
capillary, they are referred to as classic wire
loops, which produce a rigid, refractile thickening
of the glomerular capillary wall in hematoxylin-
eosin stained sections,
16. Lupus nephritis class IV.
Trichrome stain highlights the
presence of global subendothelial
fuchsinophilic deposits. (Masson's
trichrome, ×500.)
Lupus nephritis class IV. In
addition to wire-loop deposits,
there are segmental intraluminal
deposits forming hyaline
thrombi.•(H&E; ×320.)
17. • Active class III or IV lupus
nephritis have large
intracapillary immune
deposits forming hyaline
thrombi;
• Can be differentiated from
true fibrin thrombi by
special stains for fibrin
(modified Fraser Lendrum
stain and phosphotungstic
acid hematoxylin [PTAH]
stain) and by staining for
fibrin-related antigens by
immunofluorescence
Lupus nephritis class IV. The
hyaline thrombi stain red against
the blue-staining glomerular
capillary walls. (Masson's
trichrome, ×500
18. • 2. Glomerular
proliferations:
• May be: mesangial,
endocapillary, and
extracapillary
• Endocapillary
proliferation can be
defined as a proliferation
of endothelial cells and
mesangial cells together
with infiltrating
leukocytes (including
mononuclear or
polymorphonuclear
leukocytes) that
significantly narrows or
occludes the glomerular
capillary lumen.
Lupus nephritis class IV. There is
relatively uniform diffuse and
global endocapillary
proliferation. (H&E; ×100.)
19. • 3. Glomerular Necrosis:
feature of class III or IV lupus
nephritis ; never observed in
pure mesangial proliferative
(class II) or membranous (class
V) lupus nephritis.
• Consists of a focus of smudgy
fibrinoid obliteration of the
glomerular tuft, which is often
associated with any or all of the
following: deposition of
intracapillary fibrin,
glomerular basement
membrane rupture or gap
formation, and apoptosis of
infiltrating neutrophils
forming pyknotic or
karyorrhectic nuclear
debris
Lupus nephritis class III.
There is segmental fibrinoid
necrosis with neutrophil
infiltration and pyknosis.
(H&E; ×500.)
20. • 4. Hematoxylin Bodies:
they are rounded, smudgy,
lilac-staining structures,
seen as cells with
degenerated aspect;
probably they represent
degenerated nuclei and
correspond to LE cells
described in the blood of
patients with SLE.
• Only truly pathognomonic
lesion in lupus nephritis but
very uncommon(2%).
Lupus nephritis class IV.
Several glomerular
capillaries contain
hematoxylin bodies.
Another lobule contains
karyorrhectic nuclear
debris. (H&E; ×500.)
21. • 5. Cellular crescents: defined as aggregates
comprising two or more layers of
proliferating visceral and parietal
epithelial cells with infiltrating mononuclear
cells lining one fourth or more of the
interior circumference of Bowman's
capsule.(c.f. single layer of reactive
hyperplastic visceral epithelial cells commonly
encountered in glomeruli with membranous
features or undergoing sclerosis.)
• Encountered frequently in class III or IV lupus
nephritis.
22. • 6. Glomerular
Scarring: may be
focal ,segmental to
diffuse, global.
Lupus nephritis class IV. Despite aggressive
therapy, repeat renal biopsy two years later
shows progression to segmental and global
glomerulosclerosis with focal fibrous
crescents. There is marked reduction in the
degree of interstitial inflammation. (Jones
methenamine silver, ×80.)
23. Tubules and Interstitium
• In patients with nephrotic-range proteinuria,
proximal tubules are involved. There are
pesence of intracytoplasmic lipid
resorption droplets that appear as clear
vacuoles in hematoxylin-eosin preparations
because of removal of the lipid in the course of
tissue processing and protein resorption
droplets that appear eosinophilic and strongly
PAS-positive and usually trichrome red. The
latter change has been referred to as hyaline
degeneration•of the proximal tubules,
24. • Active lesion: interstitial inflammation and
edema
• Chronic lesion: tubular atrophy and interstitial
fibrosis.
• The interstitial infiltrates consist predominantly
of mononuclear leukocytes, including
lymphocytes, monocytes, and plasma cells.
• Tubulointerstitial immune deposits: seen in
diffuse proliferative lupus nephritis.
• They consist of granular, electron-dense
deposits that involve tubular basement
membranes, interstitial capillary basement
membranes, and interstitial collagen.
25. Lupus nephritis class IV.
High-power view shows a
lamellated network of
tubular basement
membrane splayed
around the tubular
basement membrane
deposits. (Electron
micrograph, ×4000.)
Lupus nephritis class IV.
The immunofluorescence
micrograph shows
abundant granular
deposits of IgG within the
tubular basement
membranes and
interstitium. (×200.)
26. • The severity of tubulointerstitial
inflammation correlates broadly with
glomerular proliferative lesions . It constitutes
one of the best morphologic correlates with the
degree of renal insufficiency and is an accurate
prognosticator of subsequent decline in renal
function.
• Tubular atrophy, at least in part the result of
interstitial inflammation, is one of the strongest
predictors of renal failure , as it is in many
other glomerular diseases
27. Vascular Lesions
Arteriosclerosis and arteriolosclerosis
Uncomplicated vascular immune deposits
Noninflammatory necrotizing vasculopathy (so-
called lupus vasculopathy)
Thrombotic microangiopathy
Associated with HUS/TTP syndrome
Associated with antiphospholipid antibodies
Associated with scleroderma/mixed connective
tissue disease
Necrotizing vasculitis (PAN type)
28. Uncomplicated Vascular Immune
Deposits.
• Most common renal vascular
lesion in SLE is immune complex
deposition in the walls of small
arteries and arterioles; deposition
occurs to a lesser extent in veins
• Diagnosis requires the
demonstration of granular
deposits of immunoglobulin (IgG,
IgM, and IgA in various
combinations), often associated
with C1q or C3.
Lupus nephritis class IV.
The fluorescence
micrograph shows
abundant granular staining
for IgG within the intima
and media of an
interlobular artery. (×
400.)
29. Noninflammatory Necrotizing
Vasculopathy
• Affects predominantly preglomerular arterioles
in the setting of severe active class IV lupus
nephritis.
• The affected vessels are severely narrowed and
sometimes occluded by abundant intimal and
luminal deposits of glassy eosinophilic material
that may extend into the media.
• This material is usually fuchsinophilic in
trichrome-stained preparations
30. Lupus
vasculopathy. A
double panel
shows occlusion of
preglomerular
arterioles by
eosinophilic
deposits (left) that
stain positive with
Lendrum stain for
fibrin (right). (×
500.)
31. Thrombotic Microangiopathy
• Most commonly affect preglomerular arterioles
and interlobular arteries
• By LM, the affected vessels are occasionally
narrowed or occluded by intraluminal fibrin
thrombi, which may be associated with
endothelial swelling and denudation
• By IFM, the affected vessels usually reveal
intense, dominant staining for fibrin-related
antigens, with variable positivity for IgM and C3.
32. Renal Vasculitis
• Least common vascular lesion
• There is leukocyte infiltration of vessel walls,
often accompanied by necrosis.
• IFM: strong staining for fibrin-related antigens
with weak and more variable staining for
immunoglobulin and complement;
• representing nonspecific trapping of plasma
proteins in areas of necrosis.
33. Immunofluorescence
• Immunostaining for IgG in more than 90% of
cases; there is IgA and IgM staining in 60-70%
of cases.
• The presence of the three immunoglobulins (Igs)
with C3 and C1q is well-known as “full house”
pattern, and it is very characteristic of lupus
nephritis.
34. Electron microscopy
• Electron dense deposits are demonstrated with a
distribution similar to the one of the immune
deposits detected by IF, according to the class.
35. Classification of Lupus Nephritis
• 2003 International Society of Nephrology/Renal
Pathology Society (ISN/RPS) classification of
lupus glomerulonephritis (LGN)
• Class I: minimal mesangial lupus nephritis
• Normal glomeruli by light microscopy (LM), but
mesangial immune deposits by immunofluorescence (IF)
and/or electron microscopy (EM)
• Class II: mesangial proliferative lupus nephritis
• Purely mesangial hypercellularity of any degree or
mesangial matrix expansion by LM with mesangial
immune deposits; may be a few isolated subepithelial
and/or subendothelial deposits by IF and/or EM, but not
visible by LM
36. Lupus nephritis class I. The
glomerulus is normal in
cellularity, and the glomerular
basement membranes are
unremarkable. (PAS; ×500.)
Lupus nephritis class II. There is
mild, global, mesangial
hypercellularity with thin capillary
loops. (H&E, ×500.)
37. • Class III: focal lupus nephritis
• Active or inactive focal, segmental or global endo- or
extracapillary glomerulonephritis involving <50% of
all glomeruli, typically with focal subendothelial
immune deposits,with or without mesangial
alterations
• III (A) Active lesions: focal proliferative LGN
• III (A/C) Active and chronic lesions: focal
proliferative and sclerosing LGN
• III (C) Chronic inactive lesions with glomerular
scars: focal sclerosing LGN
38. Lupus nephritis class III. A
low-power view shows the
focal and segmental
distribution of the
endocapillary proliferation,
with some overlying
crescents. Endocapillary
proliferation affected less
than 50% of the total
glomeruli in this biopsy.
(Jones methenamine silver
stain; ×40.)
Lupus nephritis class III. There is
segmental obliteration of
glomerular capillary lumina by
endocapillary proliferation,
including infiltrating leukocytes,
with associated fibrinoid necrosis.
The adjacent lobules display mild
mesangial hypercellularity. (H&E;
×400.)
39. • Class IV: diffuse lupus nephritis
• Active or inactive diffuse, segmental or global endo- or extracapillary
glomerulonephritis involving ≥50% of all glomeruli, typically with diffuse
subendothelial immune deposits, with or without mesangial alterations.
This class is divided into diffuse segmental (IVS) lupus nephritis when
≤50% of the involved glomeruli have segmental lesions, and diffuse global
(IV-G) lupus nephritis when ≥50% of the involved glomeruli have global
lesions.
• IV-S (A) Active lesions: diffuse segmental proliferative lupus nephritis
• IV-G (A) Active lesions: diffuse global proliferative lupus nephritis
• IV-S (A/C) Active and chronic lesions: diffuse segmental proliferative and
sclerosing lupus nephritis
• IV-G (A/C) Active and chronic lesions: diffuse global proliferative and
sclerosing lupus nephritis
• IV-S (C) Chronic inactive lesions with scars: diffuse segmental sclerosing
lupus nephritis
• IV-G (C) Chronic inactive lesions with scars: diffuse global sclerosing
lupus nephritis
40. Lupus nephritis class IV-G. There is
diffuse and global endocapillary
proliferation involving all the
glomeruli in this biopsy. (H&E, ×
180).
Lupus nephritis class IV. The low-
power immunofluorescence
micrograph shows intense, diffuse
staining for IgG in the glomerular
mesangium and peripheral capillary
loops, consistent with a
subendothelial distribution. (×120.)
41. Lupus nephritis class IV. This
example has diffuse wire-loop
deposits without appreciable
endocapillary proliferation.
(Masson's trichrome, ×600.)
Wire-loop deposit. By
immunofluorescence there is a
large subendothelial deposit that
conforms to the contour of the
glomerular basement membrane,
producing a smooth comma-
shaped outer contour. (×1000.)
42. • Class V: membranous lupus nephritis
• Global or segmental subepithelial immune deposits
or their morphologic sequelae by LM and by IF or
EM, with or without mesangial alterations
• Class V lupus nephritis may occur in combination
with class III or IV, in which case both will be
diagnosed
• Class V may show advanced sclerosis
• Class VI: advanced sclerosing lupus
nephritis
• >90% of glomeruli globally sclerosed without
residual activity
43. • Lupus nephritis class V . There
are heavy mesangial immune
deposits of IgG with more
delicate granular subepithelial
deposits.(Immunofluorescence
micrograph, ×600.)
Lupus nephritis class V . There is
regular thickening and rigidity of
the glomerular capillary walls
accompanied by global mesangial
hypercellularity. (H&E; ×500.)
44. • Indicate the proportion of glomeruli with active and
with sclerotic lesions in class III.
• Indicate the proportion of glomeruli with fibrinoid
necrosis and/or cellular crescents in class IV.
• Class V may occur in combination with class III or
IV, in which case both will bediagnosed.
• Note: Indicate the grade (mild, moderate, severe),
tubular atrophy, interstitial inflammation and
fibrosis, severity of arteriosclerosis, or other
vascular lesions
45. Lupus nephritis class VI. Extensive glomerular sclerosis shows
vestiges of fibrous crescents. The global sclerosis affected more
than 90% of glomeruli in this biopsy. Several glomeruli pictured
here are segmentally sclerotic. Atrophic tubules alternate with
groups of compensatorily hypertrophied tubules. (Masson's
trichrome, ×80.)
46.
47. Definition of active and chronic glomerular lesions
according to the
2003 ISN/RPS classification of lupus nephritis
• Active lesions(0-24)
• Endocapillary hypercellularity
(0-3 +)
• Leukocyte Infiltration (0-3 +).
Neutrophil exudation is defined
as more than two neutrophils
per glomerulus.
• Subendothelial hyaline deposits
(0-3 +)
• Fibrinoid necrosis/karyorrhexis
(0-3 +)×2
• Cellular crescents (0-3 +)×2
• Interstitial Inflammation (0-3
+)
• Chronic lesions(0-12)
• Glomerular sclerosis
(segmental, global)(0-3)
• Interstitial fibrosis(0-3)
• Tubular atrophy (0-3)
• Fibrous crescents(0-3)
0, absent;
1+, less than 25% of glomeruli
affected;
2+, 25% to 50% of glomeruli affected;
3+, more than 50% of glomeruli
affected
48. DIFFERENTIAL DIAGNOSIS
• Any immune complex GN
• IgA nephropathy
• HSP
• C1q nephropathy
• Idiopathic membranous GN(In lupus-associated
membranous GN, there are
mesangial,subendothelial deposit,TID and ANA.
IF characteristically shows a “full house”
pattern.)
49. Pathogenesis
• Three major mechanisms of immune deposition
in the kidney have been identified:
• (a) binding of autoantibodies to intrinsic
glomerular antigens,
• (b) binding of autoantibodies to nonglomerular
autoantigens that have been planted in the
glomerulus, and
• (c) deposition of preformed circulating immune
complexes.
50. • Role of Immunoglobulin :
• predominant immunoglobulin isotype in
glomerular deposits is IgG
• other immunoglobulin classes (IgM, IgA, and
IgE) may codeposit in glomeruli
51. • Role of Electric Charge of
Immunoglobulin:
• Charge characteristics Igs probably play a role in
the localization of immune deposits in lupus
nephritis, they are not the major determinant of
susceptibility to nephritis
52. • Autoantibody Specificity and Cross-
Reactivity for Glomerular Constituents:
• antibodies to nuclear constituents (i.e., anti-
ssDNA, dsDNA, histone, RNP, and
nucleosomes),
• cytoplasmic constituents (i.e., anti-Sm), and
• cell membrane antigens (i.e., APL and
antiendothelial antibodies).
53. • lupus autoantibodies bind in situ to normal
glomerular cellular or matrix components and
that these cross-reactivities may play a major
role in the development of nephritis
54. • Role of Binding of Autoantigens to
Glomerular Constituents:autoantigens may
first become planted within the glomerulus
through particular charge or other physical
interactions.
• Once planted in the glomerulus, they are then
free to interact with circulating autoantibody,
causing the formation of immune complexes in
situ
55. Antibodies to nucleosomes (DNA bound
to histones)
• During apoptosis, the organized cleavage of
chromatin leads to clustering of nucleosomes on the
surface of apoptotic cells
• Normally, these apoptotic bodies are efficiently
cleared by effector cells before nucleosomes can be
released into the circulation
• In SLE, there is evidence of increased or delayed
apoptosis or reduced clearance of apoptotic cells,
leading to increased exposure of immunogenic
nucleosomes to the immune system and the ensuing
formation of nucleosome-specific T cells and
antinucleosome autoantibodies
56.
57. • Role of Deposition of Preformed Immune
Complexes: the circulating immune complex
load may predispose the patient to particular
patterns of lupus nephritis
• Small amounts of intermediate-sized, high-
avidity complexes=mesangial pattern
• Larger quantities of intermediate-sized
complexes or large complexes =subendothelial
deposition
58. • Cellular and Coagulation Factors:
• Deposition of immune complex
activation of cytokine networks
leukocyte recruitment,
cellular proliferation,
matrix production, and
intravascular coagulation
GLOMERULAR INJURY
59. • Genetic Factors: several class I and class II
MHC genes are involved
• Epidemiologic Factors:
• Race: african american> caucasians
• Sex: F>M
• Klinefelter's syndrome> hyperestrogenic state>
increased bindining of anti-Ro and anti-La Ab
60. • B-Cell and T-Cell Abnormalities:
• Lupus have enhanced B-cell proliferation,
activation, and immunoglobulin production, and the
number of Ig-secreting B cells in the peripheral
blood is increased .
• Paradoxically, the number of total B lymphocytes in
the peripheral blood is often reduced
• B cells secrete IL-2,IL-6,IL-10, TGF, TNF,IFN.
• B cells specific for nuclear antigens may get second
signals from TLRs and may be activated, resulting in
increased production of antinuclear autoantibodies.
• Impaired T-cell response to mitogens, antigens, and
autologous or allogeneic class II MHC molecules
• CD8+ cells from patients with SLE are often unable
to downregulate polyclonal immunoglobulin
production and synthesis of autoantibodies
61. • Antibody Specificity:
• The production of autoantibodies, especially
ANA, is a defining feature of SLE and probably
an integral pathogenetic factor.
• Clinical manifestation of ANA is LE cell.
• The LE cell is a neutrophil or monocyte that has
phagocytosed a nucleus, producing a purplish
inclusion in a process that is mediated by
antibody to the nucleosomal
deoxyribonucleoprotein histone complex
• Antibodies to dsDNA are the most specific for
SLE
• Anti histone and anti DNP Abs(against
nucleosome) are most common in SLE.
62. • Complement Abnormalities:
• Commonly involve C1,C2 and C4. Due to null
allele.
• Low C1q levels have been associated with
proliferative lupus nephritis classes III and IV
and may predict the occurrence of renal flares.
63. Demonstration of LE cell
• Twenty millilitres of venous blood are
defibrinated by agitation in a universal (1-oz.
bottle) container holding a bent paper clip.
• The defibrinated blood is transferred to a
conical tube and centrifuged for five minutes
at 1,800 r.p.m.
• The upper cellular layer is transferred by a
Pasteur pipette to a Wintrobe tube, which is
again centrifuged at 1,800 r.p.m. for five
minutes.
• Smears are made from the buffy coat, and
stained by the Leishman method.
• The number of L.E. cells per 500 leucocytes is
then determined.
• The inclusions show varying grades of density
and of colour from deep blue to pink.
64. References
• Sternberg's Diagnostic Surgical Pathology, 5th
ed. 2010, Pg
• Heptinstall's Pathology of the Kidney (2-Volume
Set), 6th ed
• Fogo_Fundamental of Renal Pathology