Glomerulonephritides are diseases of the glomeruli that constitute major problems in nephrology. The glomerulus consists of a network of capillaries surrounded by epithelial cells. Glomerular diseases can be primary or secondary to other systemic diseases. The pathogenesis involves immune mechanisms such as deposition of immune complexes or antibodies reacting with antigens in the glomerulus. This causes inflammation and injury through activation of complement and recruitment of leukocytes. Conditions like minimal-change disease and focal segmental glomerulosclerosis are common causes of nephrotic syndrome, characterized by massive proteinuria and edema.
Let's learn the pharmacology related to nephrotic syndrome - features of nephrotic syndrome with underlying mechanisms, objectives of treatment, and management of the nephrotic syndrome.
Let's learn the pharmacology related to nephrotic syndrome - features of nephrotic syndrome with underlying mechanisms, objectives of treatment, and management of the nephrotic syndrome.
most of the glomerular diseases , either primary or secondary..touching all the aspects including light microscopy, electron microscopy and immunoflourescence.
Rapidly progressive glomerulonephritisajith joseph
Rapidly progressive glomerulonephritis (RPGN) is a syndrome of the kidney that is characterized by a rapid loss of renal function,[4][5] (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months)[5] with glomerular crescent formation seen in at least 50%[5] or 75%[4] of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute renal failure[6] and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus or granulomatosis with polyangiitis; the remaining cases are idiopathic. Regardless of the underlying cause, RPGN involves severe injury to the kidneys' glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent-shaped scars)
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
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
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
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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.
3. 3
Light micrograph of a normal glomerulus. There are only 1 or 2 cells per capillary tuft, the capillary
lumens are open, the thickness of the glomerular capillary wall (long arrow) is similar to that of the
tubular basement membranes (short arrow), and the mesangial cells and mesangial matrix are located
in the central or stalk regions of the tuft (arrows). Courtesy of Helmut G Rennke.
4. 4 Electron micrograph of a normal glomerular capillary loop showing the fenestrated endothelial cell (Endo), the glomerular
basement membrane (GBM), and the epithelial cells with its interdigitating foot processes (arrow). The GBM is thin and no
5. Glomerular diseases constitute some of the
major problems encountered in nephrology;
chronic glomerulonephritis is one of the
most common causes of chronic kidney
disease in humans.
The glomerulus consists of an anastomosing
network of capillaries invested by two
layers of epithelium.
6. The glomerular capillary wall is the filtration unit
and consists of the following structures:
A thin layer of fenestrated endothelial cells.
A glomerular basement membrane (GBM) with a
central layer, the lamina densa, and thinner
peripheral layers, the lamina rara interna and
lamina rara externa.
7. The visceral epithelial cells (podocytes)
The entire glomerular tuft is supported by
mesangial cells lying between the capillaries.
8. Glomerular Diseases
Primary Glomerular Diseases
Minimal-change disease
Focal and segmental glomerulosclerosis
Membranous nephropathy
Acute postinfectious GN
Membranoproliferative GN
IgA nephropathy
Chronic GN
9. Glomerulopathies Secondary to Systemic
Diseases
Lupus nephritis (systemic lupus erythematosus)
Diabetic nephropathy
Amyloidosis
GN secondary to lymphoplasmacytic disorders
Goodpasture syndrome
Microscopic polyangiitis
12. Pathogenesis of Glomerular Diseases
Immune mechanisms underlie most types
of primary glomerular diseases and many of
the secondary glomerular diseases.
GN can be induced by antibodies, and
glomerular deposits of immunoglobulins,
often with various components of
complement, are found frequently in patients
with glomerulonephritis.
14. Two forms of antibody-associated injury
have been established:
(1) injury resulting from deposition of
soluble circulating antigen-antibody
complexes in the glomerulus.
15. (2) injury by antibodies reacting in situ
within the glomerulus, either with insoluble
fixed (intrinsic) glomerular antigens or with
molecules planted within the glomerulus
In addition, antibodies directed against
glomerular cell components may cause
glomerular injury.
16.
17. Nephritis Caused by Circulating Immune
Complexes
Antigen-antibody complexes trapped in the
glomeruli, where they produce injury,
through the activation of complement and
the recruitment of leukocytes.
Injury may also occur through the
engagement of Fc receptors on leukocytes
independent of complement activation.
18. The glomerular lesions usually consist of
leukocytic infiltration (exudation) into
glomeruli and variable proliferation of
endothelial, mesangial, and parietal
epithelial cells.
19. Electron microscopy reveals the immune
complexes as electron-dense deposits or
clumps that lie at one of three sites: in the
mesangium, between the endothelial cells
and the GBM (subendothelial deposits), or
between the outer surface of the GBM and
the podocytes (subepithelial deposits).
Deposits may be located at more than one
site in a given case.
20. Immune complexes may eventually be
degraded or phagocytosed, mostly by
infiltrating leukocytes and mesangial cells,
and the inflammatory changes may then
subside.
21.
22. Nephritis Caused by In Situ Immune
Complexes
Antibodies react directly with fixed or
planted antigens in the glomerulus.
Spontaneous anti-GBM antibody GN in
humans results from the formation of
autoantibodies directed against the GBM.
23. Deposition of these antibodies creates a
linear pattern of staining when the bound
antibodies are visualized with
immunofluorescence microscopy,
24. The basement membrane antigen
responsible for classic anti-GBM antibody
GN is a component of the noncollagenous
domain of the α3 chain of collagen type IV.
Sometimes the anti-GBM antibodies cross-
react with basement membranes of lung
alveoli, resulting in simultaneous lung and
kidney lesions (Goodpasture syndrome).
25. Antibodies may react in situ with
previously "planted" nonglomerular
antigens, which may localize in the kidney
by interacting with various intrinsic
components of the glomerulus.
Most of these planted antigens induce a
granular pattern of immunoglobulin
deposition as seen by immunofluorescence
microscopy.
26. factors affecting glomerular localization of
antigen, antibody, or complexes includes
the molecular charge and size.
27. Studies show that complexes deposited in
the endothelium or subendothelium elicit an
inflammatory reaction in the glomerulus
with infiltration of leukocytes.
Antibodies directed to epithelium and
subepithelium are largely noninflammatory
and elicit lesions similar to those of
Heymann nephritis or membranous
nephropathy.
28. Cell-Mediated Immune
Glomerulonephritis
T cell-mediated injury may account for the
instances of GN in which either there are no
deposits of antibodies or immune complexes
or the deposits do not correlate with the
severity of damage.
29. Mediators of Immune Injury
A major pathway of antibody-initiated
injury is complement-leukocyte-mediated.
Activation of complement leads to the
generation of chemotactic agents (mainly
C5a) and the recruitment of neutrophils and
monocytes.
30. Neutrophils release proteases, which cause
GBM degradation; oxygen-derived free
radicals, which cause cell damage; and
arachidonic acid metabolites, which
contribute to reduction in GFR.
31. Effect of the C5-C9 lytic component of
complement, which causes epithelial cell
detachment and stimulates mesangial and
epithelial cells to secrete mediators of cell
injury.
33. The membrane attack complex also up-regulates
transforming growth factor-β receptors on
podocytes; TGF-β stimulates synthesis of
extracellular matrix, giving rise to altered GBM
composition and thickening.
Antibodies directed to glomerular cell antigens
may also be directly cytotoxic to glomerular
cells.
34. Other mediators of glomerular damage include;
(1) monocytes and macrophages - release a vast
number of biologically active molecules
(2) platelets - release prostaglandins and growth factors
35. (3) resident glomerular cells (epithelial, mesangial, and
endothelial) - secrete mediators such as cytokines
(interleukin 1), arachidonic acid metabolites, growth
factors, nitric oxide, and endothelin
(4) fibrin-related products
36. Other Mechanisms of Glomerular Injury
Podocyte Injury - Such injury is reflected
by morphologic changes in the podocytes.
Nephron Loss - Once any renal disease,
glomerular or otherwise, destroys sufficient
functioning nephrons to reduce the GFR to
30% to 50% of normal, progression to end-
stage renal failure often proceeds.
37. The Nephrotic Syndrome
Refers to a clinical complex that includes
the following:
(1) massive proteinuria, with daily protein
loss in the urine of 3.5 gm or more in adults
(2) hypoalbuminemia, with plasma albumin
levels less than 3 gm/dL
(3) generalized edema
(4) hyperlipidemia and lipiduria.
38. The initial event is a derangement in the
capillary walls of the glomeruli, resulting in
increased permeability to plasma proteins.
39. In children 1 to 7 years of age, nephrotic
syndrome is almost always caused by a
lesion primary to the kidney, whereas
among adults it is often due to renal
manifestations of a systemic disease.
40. Causes of Nephrotic Syndrome
Primary Glomerular Disease
Membranous GN
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative GN
IgA nephropathy
44. Minimal-Change Disease (Lipoid
Nephrosis
Most frequent cause of the nephrotic
syndrome in children
Characterized by glomeruli that have a
normal appearance by light microscopy but
show diffuse effacement of podocyte foot
processes when viewed with the electron
microscope
Most common between ages 1 and 7 years.
45. The cells of the proximal convoluted
tubules are often heavily laden with protein
droplets and lipids, secondary to tubular
reabsorption of the lipoproteins passing
through the diseased glomeruli.
46. Clinical Course
Development of the nephrotic syndrome in
an otherwise healthy child
Renal function is preserved in most
individuals
The protein loss is usually confined to the
smaller serum proteins, chiefly albumin
(selective proteinuria)
47.
48. More than 90% of cases respond to a short
course of corticosteroid therapy;proteinuria
recurs in more than two-thirds of the initial
responders, some of whom become steroid
dependent.
Less than 5% develop chronic renal failure
after 25 years
The prognosis in children with this disorder
is good.
49. Focal and Segmental Glomerulosclerosis
Characterized histologically by sclerosis
affecting some but not all glomeruli (focal
involvement) and involving only segments
of each affected glomerulus.
50. Occur
(1) in association with other conditions,
such as human immunodeficiency virus
infection or heroin abuse (human
immunodeficiency virus nephropathy,
heroin nephropathy)
(2) as a secondary event in other forms of
GN (e.g., immunoglobulin A [IgA]
nephropathy)
51. (3) as a maladaptation after nephron loss
(4) in inherited or congenital forms
resulting from mutations affecting
cytoskeletal or related proteins expressed in
podocytes
(5) as a primary disease.
52. There is a higher incidence of hematuria
and hypertension in persons with this lesion
Proteinuria is nonselective, and response to
corticosteroid therapy is poor
53. At least 50% of individuals with FSGS
develop end-stage renal failure within 10
years of diagnosis.
Adults fare even less well than children.
54. injury to the podocytes is thought to
represent the initiating event of primary
FSGS.
The deposition of hyaline masses in the
glomeruli represents the entrapment of
plasma proteins and lipids in foci of injury
where sclerosis develops.
55. IgM and complement proteins commonly
seen in the lesion are also believed to result
from nonspecific entrapment in damaged
glomeruli.
56. Morphology
The affected glomeruli exhibit increased
mesangial matrix, obliterated capillary
lumens, and deposition of hyaline masses
(hyalinosis) and lipid droplets.
Occasionally, glomeruli are completely
sclerosed (global sclerosis).
57. Immunofluorescence microscopy -
nonspecific trapping of immunoglobulins,
usually IgM, and complement in the areas
of hyalinosis.
Electron microscopy - the podocytes
exhibit effacement of foot processes, as in
MCD.
58. Progression leads to global sclerosis of the
glomeruli with pronounced tubular atrophy
and interstitial fibrosis.
Morphologic variant called collapsing
glomerulopathy characterized by collapse
of the entire glomerular tuft and podocyte
hyperplasia can occur.
59. Clinical Course
There is little tendency for spontaneous
remission of idiopathic FSGS, and responses
to corticosteroid therapy are usually poor.
About 50% of individuals suffer renal
failure after 10 years.
60.
61. Membranous Nephropathy
(Membranous Glomerulonephritis)
Most common between 30 and 50 years of
age.
Characterized morphologically by the
presence of subepithelial immunoglobulin-
containing deposits along the GBM.
Well-developed cases show diffuse
thickening of the capillary wall.
62. Idiopathic in about 85% of cases.
Remainder (secondary membranous
nephropathy), secondary to other disorders,
including:
(1) infections (chronic hepatitis B, syphilis,
schistosomiasis, malaria);
(2) malignant tumors, particularly
carcinoma of the lung and colon and
melanoma;
63. (3) SLE and other autoimmune conditions;
(4) exposure to inorganic salts (gold,
mercury);
(5) drugs (penicillamine, captopril,
nonsteroidal anti-inflammatory agents).
64. Pathogenesis
Membranous GN is a chronic immune
complex nephritis.
Although circulating complexes of known
exogenous (e.g., hepatitis B virus) or
endogenous (DNA in SLE) antigen can
cause membranous nephropathy, it is now
thought that most idiopathic forms are
induced by antibodies reacting in situ to
endogenous or planted glomerular antigens.
65. The membrane attack complex causes
activation of glomerular mesangial cells
and podocytes, inducing them to liberate
proteases and oxidants that can damage
capillary walls, with consequent
perturbations in filtration.
66. Morphology
H&E stain - diffuse thickening of the
GBM.
By electron microscopy - subepithelial
deposits.
The podocytes show effacement of foot
processes.
67. The glomeruli can become sclerosed.
Immunofluorescence microscopy shows
granular deposits of immunoglobulins
and complement along the GBM.
68. Clinical Course
Proteinuria is nonselective, with urinary loss
of globulins and smaller albumin molecules,
and does not usually respond to
corticosteroid therapy.
69.
70. Membranoproliferative
Glomerulonephritis
Manifest histologically by alterations in the
GBM and mesangium and by proliferation
of glomerular cells.
Some individuals present only with
hematuria or proteinuria in the non-
nephrotic range; others have a combined
nephrotic-nephritic picture.
71. There are two major types of MPGN (I and
II) type I being more common (about 80%
of cases).
72. Pathogenesis
Most cases of type I MPGN seem to be
caused by circulating immune complexes,
but the inciting antigen is not known.
Type I MPGN also occurs in association
with hepatitis B and C antigenemia, SLE,
infected atrioventricular shunts, and extra-
renal infections with persistent or episodic
antigenemia.
73. The pathogenesis of type II MPGN, also
known as dense-deposit disease, is less
clear.
The fundamental abnormality appears to be
excessive complement activation, which
may be caused by several mechanisms not
involving antibodies.
74. Morphology
The glomeruli are large, with an accentuated
lobular appearance, and show
proliferation of mesangial and endothelial
cells as well as infiltrating leukocytes
The GBM is thickened, and the glomerular
capillary wall often shows a double contour,
or "tram track," appearance, especially
evident in silver or periodic acid-Schiff
(PAS) stains.
75. This is caused by "splitting" of the GBM
due to the inclusion within it of processes of
mesangial and inflammatory cells extending
into the peripheral capillary loops
76. Type I MPGN is characterized by discrete
subendothelial electron-dense deposits.
By immunofluorescence microscopy, C3 is
deposited in an irregular granular pattern,
and IgG and early complement components
(C1q and C4) are often also present
77. In type II lesions the lamina densa and the
subendothelial space of the GBM are transformed into
an irregular, ribbon-like, extremely electron-dense
structure, resulting from the deposition of material of
unknown composition, giving rise to the term dense-
deposit disease.
C3 is present in irregular chunky and segmental linear
foci in the basement membranes and in the mesangium
in characteristic circular aggregates (mesangial rings).
78.
79. Clinical Course
The principal mode of presentation (in 50%∼
of cases) is the nephrotic syndrome. The
prognosis of MPGN is generally poor.
Dense-deposit disease has a worse
prognosis, and it tends to recur in renal
transplant recipients.
80. The Nephritic Syndrome
The nephritic syndrome is a clinical
complex, usually of acute onset,
characterized by;
(1) hematuria with dysmorphic red cells and
red blood cell casts in the urine
(2) some degree of oliguria and azotemia
(3) hypertension.
81. Lesions that cause the nephritic syndrome
have in common proliferation of the cells
within the glomeruli, accompanied by a
leukocytic infiltrate. The inflammatory
reaction injures the capillary walls,
permitting escape of red cells into the urine,
and induces hemodynamic changes that
lead to a reduction in the GFR.
82. Poststreptococcal Glomerulonephritis
Subacute Bacterial Endocarditis
Lupus Nephritis
Antiglomerular Basement Membrane Disease
IgA Nephropathy
ANCA Small Vessel Vasculitis
Membranoproliferative Glomerulonephritis
Mesangioproliferative Glomerulonephritis
83. Poststreptococcal glomerulonephritis is an
immune-mediated disease involving:
Streptococcal antigens
Circulating immune complexes
Activation of complement in association with
cell-mediated injury.
84. Poststreptococcal glomerulonephritis is
prototypical for acute endocapillary
proliferative glomerulonephritis.
Acute poststreptococcal GN
• 90% of cases affect children between the ages of 2
and 14 years
• 10% of cases are patients older than 40
85. The classic presentation is an acute nephritic
picture with hematuria, pyuria, red blood cell
casts, edema, hypertension, and oliguric renal
failure, which may be severe enough to appear
as RPGN.
Systemic symptoms of headache, malaise,
anorexia, and flank pain (due to swelling of the
renal capsule) are reported in as many as 50%
of cases.
86. Poststreptococcal glomerulonephritis caused by
impetigo and streptococcal pharyngitis:
• Impetigo: 2–6 weeks after skin infection
• Streptococcal pharyngitis: 1–3 weeks after infection
87. Treatment is supportive, with control of
hypertension, edema, and dialysis as needed.
Antibiotic treatment for streptococcal infection
should be given to all patients and their
cohabitants.
There is no role for immunosuppressive therapy,
even in the setting of crescents.
88. Overall, the prognosis is good, with permanent
renal failure being very uncommon (1–3%), and
even less so in children.
Complete resolution of the hematuria and
proteinuria in children occurs within 3–6 weeks
of the onset of nephritis.
89. The renal biopsy in poststreptococcal
glomerulonephritis demonstrates:
• Hypercellularity of mesangial and endothelial cells
• Glomerular infiltrates of polymorphonuclear
leukocytes
• Granular subendothelial immune deposits of IgG,
IgM, C3, C4, and C5-9
• Subepithelial deposits (which appear as "humps")
90.
91.
92. Endocarditis-associated glomerulonephritis is
typically a complication of subacute bacterial
endocarditis.
Particularly in patients who:
• Remain untreated for an extended period of time
• Have negative blood cultures
• Have right-sided endocarditis (IVDU)
93. Grossly, the kidneys in subacute bacterial
endocarditis have subcapsular hemorrhages
with a "flea-bitten" appearance.
Microscopy on renal biopsy reveals a focal
proliferation around foci of necrosis associated
with abundant mesangial, subendothelial, and
subepithelial immune deposits of IgG, IgM,
and C3.
94. The pathogenesis hinges on the renal deposition
of circulating immune complexes in the kidney
with complement activation.
95. Patients present with:
• Gross hematuria
• Microscopic hematuria
• Pyuria
• Mild proteinuria
• RPGN with rapid loss of renal function (less
common)
96. Primary treatment is eradication of the infection
with 4–6 weeks of antibiotics, and if
accomplished expeditiously, the prognosis for
renal recovery is good.
97.
98.
99. Rapidly Progressive (Crescentic)
Glomerulonephritis
RPGN is a clinical syndrome and not a
specific etiologic form of GN.
It is characterized by rapid and
progressive loss of renal function with
features of the nephritic syndrome,
often with severe oliguria and (if
untreated) death from renal failure
within weeks to months.
100. Regardless of the cause, the histologic
picture is characterized by the presence of
crescents (crescentic GN).
Produced in part by proliferation of the
parietal epithelial cells of Bowman's
capsule in response to injury and in
part by infiltration of monocytes and
macrophages.
102. Type II (Immune Complex)
Idiopathic
Postinfectious/infection related
Systemic lupus erythematosus
Henoch-Schönlein purpura/IgA
nephropathy
103. Type III (Pauci-Immune) ANCA
Associated
Idiopathic
Wegener granulomatosis
Microscopic angiitis
104.
105. Lupus nephritis is a common and serious
complication of systemic lupus erythematosus
(SLE) and most severe in African-American
female adolescents.
106. Thirty to fifty percent of patients will have clinical
manifestations of renal disease at the time of
diagnosis.
Sixty percent of adults and eighty percent of
children develop renal abnormalities at some
point in the course of their disease.
107. Lupus nephritis results from the deposition of
circulating immune complexes:
• Which activate the complement cascade
• Leads to complement-mediated damage
• Leukocyte infiltration
• Activation of procoagulant factors
• Release of various cytokines
108. The most common clinical sign of renal disease is
proteinuria, but hematuria, hypertension,
varying degrees of renal failure, and an active
urine sediment with red blood cell casts can all
be present.
109. Hypocomplementemia is common in patients
with acute lupus nephritis (70–90%) and
declining complement levels may herald a
flare.
Renal biopsy, however, is the only reliable
method of identifying the morphologic variants
of lupus nephritis.
110. Patients with crescents on biopsy may have a
rapidly progressive decline in renal function.
Without treatment, this aggressive lesion has the
worst renal prognosis.
111. Treatment must combine high-dose steroids with
either cyclophosphamide or mycophenolate
mofetil.
Current evidence suggests that inducing a
remission with administration of steroids and
either cyclophosphamide or mycophenolate
mofetil for 2–6 months, followed by
maintenance therapy with lower doses of the
same
112.
113.
114. Patients who develop autoantibodies directed
against glomerular basement antigens
frequently develop a glomerulonephritis
termed antiglomerular basement membrane
(anti-GBM) disease.
115. When they present with lung hemorrhage and
glomerulonephritis, they have a pulmonary-
renal syndrome called Goodpasture's
syndrome.
116. Goodpasture's syndrome appears in two age
groups:
• Young men in their late 20s
• Men and women in their 60–70s
Disease in the younger age group is usually
explosive:
• Hemoptysis
• Sudden fall in hemoglobin
• Fever
• Dyspnea
• Hematuria
117. The performance of an urgent kidney biopsy is
important in suspected cases of Goodpasture's
syndrome to confirm the diagnosis and assess
prognosis.
Renal biopsies typically show focal or segmental
necrosis that later, with aggressive destruction
of the capillaries by cellular proliferation, leads
to crescent formation in Bowman's space
118. The presence of anti-GBM antibodies and
complement is recognized on biopsy by linear
immunofluorescent staining for IgG (rarely
IgA).
119. Prognosis at presentation is worse if the following
• >50% crescents on renal biopsy with advanced
fibrosis
• Serum creatinine is >5–6 mg/dL
• Oliguria is present
• Need for acute dialysis
120. Patients with advanced renal failure who present
with hemoptysis should still be treated for their
lung hemorrhage, as it responds to
plasmapheresis and can be lifesaving.
Treated patients with less severe disease typically
respond to 8–10 treatments of plasmapheresis
accompanied by oral prednisone and
cyclophosphamide in the first 2 weeks.
121.
122.
123. IgA nephropathy is an immune complex-
mediated glomerulonephritis defined by the
presence of diffuse mesangial IgA deposits
often associated with mesangial
hypercellularity.
124. IgA nephropathy is one of the most common
forms of glomerulonephritis worldwide.
There is a male preponderance, a peak incidence
in the second and third decades of life, and rare
familial clustering.
125. Deposits of IgA are also found in the glomerular
mesangium in a variety of systemic diseases,
including:
• Chronic liver disease
• Crohn's disease
• Gastrointestinal adenocarcinoma
• Chronic obstructive bronchiectasis
• Idiopathic interstitial pneumonia
• Dermatitis herpetiformis
• Mycosis fungoides
• Leprosy
• Ankylosing spondylitis
126. The two most common presentations of IgA
nephropathy are recurrent episodes of
macroscopic hematuria during or immediately
following an upper respiratory infection in
children (Henoch-Schönlein purpura) or
asymptomatic microscopic hematuria most
often seen in adults.
127. Rarely, patients can present with acute renal
failure and a rapidly progressive clinical
picture.
Risk factors for the loss of renal function include
the presence of hypertension or proteinuria, the
absence of episodes of macroscopic hematuria,
male, older age of onset, and more severe
changes on renal biopsy.
128. Studies of patients with IgA nephropathy support
the use of angiotensin-converting enzyme
(ACE) inhibitors in patients with proteinuria or
declining renal function.
129. When presenting as RPGN, patients typically
receive:
• Steroids
• Cytotoxic agents
• Plasmapheresis
130.
131. A group of patients with small-vessel vasculitis
(arterioles, capillaries, and venules; rarely small
arteries) and glomerulonephritis who have
serum ANCA positivity.
The antibodies are of two types:
• Anti-proteinase 3 (PR3)
• Anti-myeloperoxidase (MPO)
132. Wegener's granulomatosis (PR3)
Microscopic polyangiitis (MPO)
Churg-Strauss syndrome (MPO)
Belong to this group because they are ANCA-
positive and have a pauci-immune
glomerulonephritis with few immune
complexes in small vessels and glomerular
capillaries.
133. Induction therapy usually includes some
combination of plasmapheresis,
methylprednisolone, and cyclophosphamide.
The steroids are tapered soon after acute
inflammation subsides, and patients are
maintained on cyclophosphamide or
azathioprine for up to a year to minimize the
risk of relapse.
135. Clinically, it can present with varying degrees of
proteinuria and, commonly, hematuria.
136. Mesangioproliferative disease may be seen in:
• IgA nephropathy
• P. falciparum malaria
• Resolving postinfectious glomerulonephritis
• Lupus nephritis
137. There is little agreement on treatment, but some
clinical reports suggest benefit from use of:
• Inhibitors of the renin-angiotensin system
• Steroid therapy
• Cytotoxic agents
138. Hereditary Nephritis
Refers to a group of hereditary glomerular
diseases caused by mutations in GBM
proteins.
Best-example is Alport syndrome, in which
nephritis is accompanied by nerve deafness
and various eye disorders, including lens
dislocation, posterior cataracts, and corneal
dystrophy.
139. Morphology
Interstitial cells take on a foamy appearance
as a result of accumulation of neutral fats
and mucopolysaccharides (foam cells) as a
reaction to marked proteinuria.
With progression, there is increasing
glomerulosclerosis, vascular sclerosis,
tubular atrophy, and interstitial fibrosis.
140. Electron microscopy;
EARLY - the basement membrane of
glomeruli appears thin and attenuated.
LATE - GBM develops irregular foci of
thickening or attenuation with pronounced
splitting and lamination of the lamina
densa, yielding a "basket-weave"
appearance.