Primary glomerulonephritis refers to inflammation of the glomerular capillaries where the kidney is the only organ involved. It can present as acute nephritic syndrome, nephrotic syndrome, or isolated hematuria/proteinuria. Diagnosis involves ruling out secondary causes through labs and biopsy showing glomerular inflammation. Common primary glomerulonephritides include minimal change disease, IgA nephropathy, membranous glomerulopathy, and focal segmental glomerulosclerosis. Treatment involves controlling proteinuria and hypertension with steroids, immunosuppressants, or renin-angiotensin system blockers depending on disease classification and severity.
Nephrotic syndrome is a clinical state characterized by : Massive proteinuria ( > 40 mg /m²/hour), Hypoalbuminaemia ( < 2.5 gm/dl), Generalized edema, Hyperlipidemia ( S. cholesterol >250 mg /dl). 60%-80% present before 6 years. MCNS most commonest type of nephrotic syndrome , about 85% of idiopathic nephrotic syndrome.
Nephrotic syndrome is a clinical state characterized by : Massive proteinuria ( > 40 mg /m²/hour), Hypoalbuminaemia ( < 2.5 gm/dl), Generalized edema, Hyperlipidemia ( S. cholesterol >250 mg /dl). 60%-80% present before 6 years. MCNS most commonest type of nephrotic syndrome , about 85% of idiopathic nephrotic syndrome.
Comprender que el cliente es prioridad de nuestra empresa y que el conocimiento y aplicación de estrategias de servicio son piezas clave en esta gestión. Conocer a nivel general el proceso de satisfacción al cliente para proporcionar un servicio de excelencia.
Práctica 1 de Evaluación de Sistemas de Información del Grado en Información y Documentación. Adaptación de las cinco leyes de Ranganathan a la Biblioteca Municipal Isabel de Villena.
Etiology- genetic mutations, infection, toxin exposure, autoimmunity, atherosclerosis, hypertension, emboli, thrombosis, or diabetes mellitus.
Even after careful study, however, the cause often remains unknown, and the lesion is called idiopathic.
Inflammation of the glomerular capillaries is called glomerulonephritis.
Persistent glomerulonephritis that worsens renal function is always accompanied by interstitial nephritis, renal fibrosis, and tubular atrophy.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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!
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
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.
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.
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 lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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
2. Basicdefinitions:
Glomerulopathy: A set of disease affecting the glomeruli of
nephron.
Glomerulitis:It accounts for inflammatory conditions of
glomerulus.
Glomerulonephritis: Nephritis marked by inflammation of
glomerular capillaries.
primary: In which the kidney is the only or predominant organ
involved
Secondary: Accompanying systemic diseases.
4. D/D of glomerulonephritis to be kept when a patient
presents with the following symptoms as a whole or rarely
when alone:
Cola colored urine(1ml BLOOD in 1 l of
urine)(haemoglobinuria /myoglobinuria difference???by
Ammonium sulphate solubility test)
Change in urine output to range from anuria to polyuria
A newly onset of hypertension in patients or normotensive
patients
From bipedal edema to generalized anasarca
It can present as Acute nephritic
syndrome/Nephrotic/NephriticNephrotic/isolated
hematuria or proteinuria.
5. Confirmation of diagnosis:
Glomerular hematuria:
>3 RBC/hpf or >5RBC/microlitre
>5% RBC are Acanthocytes,providing a specificity of 95% and
sensitivity although 50%.
Accompanying RBC cast
Accompanying albumin need to be 40% of total protein to support it
Keeping in view we must rule out :
Glomerulo vascular disorders
Atheroembolic disease
Diabetes glomerulosclerosis
Basement membrane disorder
Warfarin nephropathy
8. BIOPSY BASICS
Iverson and Brun performed first renal biopsy in 1951.
Indications of renal biopsy:
a.In context of glomerulonephritis
b.Systemic diseases with kidney involvement
c.Acute kidney disease
d.Renal transplant patients
e.Undiagnosed etiology
Performed with a kidney biopsy gun (preferably 16 G) under USG
guidance while the patient is in prone position
9.
10. Generally 10-15 glomeruli are optimal,although 6-10 are
sufficient most of the time.
Biopsy is read in terms of glomerular ,tubular,vascular or
pathology in interstitium.
Safety in pregnancy??(<30 weeks)
+ In context of focal disease of Glomerulus,we need to go to
juxtamedullary glomeruli to see the earliest involvment .
Focal glomerular disesae 25
MGN Even 1
Transplant Minimum 7
Light microscopy 8-10
11. Glomerular Non
glomerular/Urologic/Urothelial
1.URINE COLOR DARK RED,BROWN,COLA ,SMOKY BRIGHT RED
2.CLOTS _ +
3.PROTEINURIA + _
4.RBC MORPHOLOGY DYSMORPHIC ISOMORPHIC
5.HTN + _
6.EDEMA + -
7.URINARY VOIDING SYMPTOMS _ +
8.BACK PAIN + +
9.F/H + _
10.UPPER RESP TRACT
SYMPTOMS,FEVER RASH
+ _
11.RFT DERRANGED GENERALLY NOT
12. • Glomerular Proteinuria:
*Generally >2g/day
*Selective index<10%
*UPEP shows albumin fraction much greater than globulin
fraction
*Albumin/B2 microglobulin ratio>1000;1
*Less conc. Of proteins like N acetyl Glucosamine,Lysozyme
etc.
1.Primary GN
2.secondary
GGN
2 DEGREE
FSGS
Glomerulonephritis
classification
13. Secondary causes of GN can be ruled out by:
CBC,Hb1ac
24 hour urine protein
Serum albumin
LDH
C3,c4 level
SPEP,free light chain Assay
Viral markers,tropical infections profile
ANA,ANCA,RA factor,cryoglobulins,APLA ,ds-DNAetc
Drugs
14.
15. EPIDEMIOLOGY
First described by Munk in 1913 as lipoid nephrosis.
Accounts for 70-90% of Nephrotic syndrome below 10yrs
10-15% of adults and more propensity in age >60 yrs too,with more
complications.
MINIMAL CHANGE DISEASE
16. • In children M:F-2:1 or 3;1,Adults?
3. PATHOLOGY AND PATHOGENESIS:
17. Effacement of foot process of podocytes(specific????) with
cytoskeleton clumping near BM.
EXTENT OF EFFACEMENT ~ DURATION OF ACTIVE NEPHROTIC SYNDROME THAN
WITH MAGNITUDE OF PROTEINURIA.
• Glomerular permiabilty factor-hemopexin/IL-13 modulated by T cells.
• Increased Ig E.
• Charge selectivity more imp.
IMMUNOFLUORESCENCE-
• Low level mesangial staining for Ig M(Irregular Focal staining for Ig M and
C3?)
CLINICAL FEATURES
Classic presentation is nephrotic syndrome
HTN(30 %children,50%in adults)
18. • Microscopic hematuria(20% children,33% adults)
• Atopy and allergy symptoms in 30-40%
• Decreased renal functions (5% in children,30% in adults)
LAB FEATURES
• Urinalysis
• Complement levels
• ESR
• Coagulation profile
• Lipid profile
• Selectivity index<10%?
• Serum Ig E levels
19. • TREATMENT
• Prednisolone-60mg /m2 in children,1mg/kg body wt (<80mg),treatment
continued for 6 weeks after complete remission(0.2gm/24 hrs) by DIPSTICK
test at home for consecutive 3 days.
• Post remission either alternate day therapy (to 40 mg /m2) or gradual
tapering (???? needed )Acute adrenal suppression may lead to relapse
• Steroid dependence(2 weeks within or during treatment aftr remission is
acheived)/frequent relapse(2 or more within 6 months)
Cyclophosphamide-2mg/kg for 8-12 weeks /alternate is
cyclosporine/tacrolimus/MMF.
Steroid resistant(up to 12 WEEKS in children and 16 weeks in adults)
• In children need to go for biopsy
• In adults or in children if its MCD,a regimen of Calcineurin inhibitors
followed by MMF .
20. Ig A NEPHROPATHY
EPIDEMIOLOGY:
• Most common GN worldwide
• Described by Berger and Hinglais in late 1960s
• Male:female-2:1 to 6:1
• 2 nd to 3rd decade
• 30-40% to ESRD.
GENETICS:
Genetic and Environmental factors both
D allele mutation of ACE gene in Asians.
6th chromosome igan1 gene
Galactosyl transferase gene ,sialyl transferase gene
Selectin cluster gene
22. • 100% stains for Ig A/50 % for Ig G/Less consipicious C3
• If C1q +Ig A+Ig G+C3---LUPUS???
• More lambda chains (kappa chains in other)/light chain deposition
disease??-kappa predominant/renal amyloidosis have lambda
predominant
Electron Microscopy-
Mesangial deposits with mesangial matrix expansion and
hypercellularity.
Light Microscopy-
37% have focal proliferative glomerulonephritis,28% have DPGN
Wide spread damage can present lupus like.
23. Pathogenesis: Abnormal sialyation of N-ACETYL
GALACTOSAMINE stops conversion ie its replacement by
galactose ,this mutation in Ig A leads to functioning as Antigen
which binds to Ig G in serum and this circulating complex deposits in
glomeruli through mesangial receptors(transferrin) Ig A1 can also
bind to mesangium but it cant lead to proliferation
ENVIROMENTAL CROSS REACTING ANTIGEN???
CLINICAL FEATURES:(synpharyngitic presentation)
• 40-50% -Macroscopic hematuria often associated dysuria
• 10% cases-Acute renal insufficiency
• 30%-Asymptomatic microscopic hematuria
• 30% new onset proteinuria and HTN
• May be nephrotic syndrome like presentation
24. Prognostic factors:
• Sustained hypertension
• Persistent proteinuria
• Impaired RFT
• Nephrotic like - all signifies Bad prognosis.
• Episodic macroscopic hematuria have good prognosis than
microscopic????(EPIOSDIC AND SELF RESOLVING)
TORONTO FORMULA???
MAP and proteinuria
Four independent parameters:
1. Mesangial hypercellularity-significant association with ESRD
2. Endocapillary hypercellularity-More benefit of immunosuppressive
3. Tubular atrophy
4. Segmental glomerulosclerosis
In IgA nephropathy there been a improved prognosis with moderate alcohol
consumption and mild jaundice.
25. Laboratory finding:
• Nephritic pres.
• Complement levels,IgA/C3 ratio,C3 fragments
• Serum Ig A levels(Increased in 50%,importance???)
Treatment Recommendations;
• For patients with proteinuria >0.5 gm/day..we need to treat
• Max tolerated ACE/ARBs to target protein excretion<0.5
• Steroids to come into practice when the prognostic factors are bad,but
GFR>60 and proteinuria >0.5after 3-6 months trial of ACEs.
• Still those with progressive renal insufficiency ,prednisolone with
cyclophosphamide followed by azathioprine should be used.
• Omega 3 fatty acids in view of their less side effect profile ,has made a
substantial benefit when used with ACE/ARBs.(12g /day)
• Recurrence after transplantation is 75-80% but graft loss is quite uncommon
except in those with bad prognostic factors.
26. MEMBRANOUS GLOMERULOPATHY
*In adult one of the commonest cause of Nephrotic syndrome.
* M:F-2:1,A:C-26:1
* Rule out secondaries-drugs,Ca lung and prostate MC,CTDs ,hep.
27. PATHOLOGY AND PATHOGENESIS
• EM-Ehrenerich and Churg staging
• Stage 1 from subepithelial deposition to stage 4 of irregular
electron dense deposition within irregular thickend BM.
28. ?MESANGIAL DEPOSITS???
• IM-Ig G most prominent followed by Ig M and Ig A,C3 also present in 95%..but not that intense.
• LM-Diffuse capillary wall thickening with absence of significant glomerular hypercellularity.
PATHOGENESIS- In situ immuncomplex depositon MC mechanism
1. Phospholipase A2 receptor of podocytes-MC 70% cases
2. Neutral endopeptidase of podocytes
3. Cationic bovine serum albumin
MC antibody involved is Ig G4
Circulating complex in SECONDARY DISEASE?
Role of complements???
• In complex deposited there is also paucity of complements,serum levels
are normal???
• Nephritogenic serums contain antibodies to react with Crry/DAF etc,less
production of factor H.
29. C/F and PROGNOSIS:
• 70-80% Nephrotic presentation,may be massive
• 10-20% Proteinuria <2 gm/day
• HTN-13-55%
SUDDEN DETRIORATION-RVT(4-52%)/CRESCENTIC/DRUGS????
35%ESRD in 10yrs,spontaneous remission(clinicians approach in MGN good
prognosis.)-35%
BAD PROGNOSIS-
Male /massive proteinuria/age>50 yrs/proteinuria >4gm for 4 months even on
treatment/uncontrolled HTN/crescentic/segmental sclerosis.
LAB FEATURES :
Routine Urine,24 hr protein,
Serum albumin???(<2)
Complement levels-NORMAL
30. TREATMENT:
Spontaneous remissions
RAAS blockers
Less than 4 gm/24 hrs no Rx/4-8gm depending upon prognostic
factors/.8gm-we need to treat.
PONTICELLI REGIMEN-Preferred now cyclophosphamide(2mg/kg/day )in
place of chlorambucil.
Other- ACTH,Rituximab,CNIs
Serum albumin<2,with no C/I to anticoagulants, we can use it.
RELAPSE-Repeat same regimen although alkylating agents can be given
once more.
31. FOCAL SEGMENTAL GLOMERULOSCLEROSIS
INTRODUCTION
• Basically a histological description but per se also refer to particular
disease
• M>F,much predominant in blacks
PATHOLOGY AND PATHOGENESIS
32. LM - Focal and segmental glomerulosclerosis
• If we don’t get it,even focal tubulointerstitial injury with glomerular hypercellularity can
be used as surrogate marker.
• Microcystic change in tubular epithelial cells
• Endothelial tubuloreticular inclusions(others HIV,SLE,Interferon alpha,pamidronate)
HISTOLOGICAL CLASSIFICATION
1.Classical variety/NOS variant-Proto type,MC
2.Cellular variant-Endocapillary hypercellualrity with capillary inclusion.
3.Tip variant-Alongside of proximal tubule, outer tip of glomerulus. Steroid responsive with
very good prognosis.
4.Collapsing variant-Torrential nephritic syndrome and rapid declining renal function.
5.Perihilar variant-Perihilar hyalinosis and sclerosis in >50%,often seen with hyperfiltration
injury .
IM-
• IM staining is only shown by sclerotic glomeruli
• EM-V imp to rule out other causes of glomerular scarring.
34. • As shown above the genetic mutations
• Black race much vulnerable due to MYH9 SNPs ,APOL1 variants(protective against
T.Brucei) on chromosome 22.
• Glomerular permeability factor??
• Parvovirus and SV40 virus.
• Glomerular damages and inciting events
C/F and PROGNOSTIC FACTORS:
• 80% Cases Nephrotic syndrome presentation
• Hematuria 50%/HTN-1/3rd cases
• Perihilar and collapsing variety early age , perihilar a/w hyperfiltration and
collapsing with torrential proteinuria
• Tip lesions –older peoples,although severe proteinuria like MCD,but most cases are
self resolving,or good remission with steroids.
• Poor prognosis are-
Black male/severe proteinuria(>10gm/day)/Interstitial fibrosis on histology/no
responsive to rx/collapsing variant
35. TREATMENT:
• Prednisolone 1mg/kg (max 80 mg) upto 16 weeks or till remission in
full dosage.If there is remission, we need to taper it to nil in 6
months.
• If we don’t get remission,prednisolone at 0.15 mg/kg to be continued
with cyclosporine(3-5 mg/kg) in two divided dosages, for 6 months.If
we get positive response continuation upto 12 months.
• If even not,we can try PEX(very good results in post
Tx),Tacrolimus,MMF.
36. POST STREPTOCCCAL
GLOMERULONEPHRITIS
EPIDEMIOLOGY:
• Peak incidence 2-6 yrs,15% cases accounts between less than 2 and more than
40 yrs.M>F
• HLA –DRw4 are susceptible ones.
• Group A Lancefield (on Carbohydrate antigen) beta hemolytic streptococci
MC type 12 and 49,other Griffith M(on protein) type strains
1,2,3,4,18,52,55,57,58,59,60,61 are highly nephritogenic.Type 2,49,55,57 and 60
are associated with post impetigo,M type 49 can lead to nephritis after
both.Type C(Recent epidemic with strept. Zooepidemicus) and G has also
been implicated in few cases.
• Risk is about up to 15% with nephritogenic strains.(SEEGAL &EARL)
• Impetigo a/w epidemic PSGN ,Pharyngitic with sporadic mainly.
37.
38. C/F:
• Post Pharyngitic phase-7-21days
• Post impetigo-14-21 days
• Synpharyngitic <7 days.
• Classic nephritic presentation,HTN in around 75%,edema is presenting symptom in
2/3rd,with present in almost 90% cases.Flank pain is associated in about 50% cases
• Clinical manifestation usually resolves in 1-2 weeks,with complete resolution of
microscopic hematuria and proteinuria can take up to 8 weeks.
• Together PSGN and Rheumatic fever very rare but can be possible.
LAB FINDING:
• R/E Urine- 5% of children and 20% adults have nephrotic range proteinuria.
• Streptozyme test (Anti streptococcal antibody assays.),CULTURE(10-70%),ASO
TITRE(30%),Anti DNAse-70%,Anti hyaluronidase -40%
• ASO titres (2/3rd of pharyngitic and 1/3rd of impetigo)and those not producing
,Anti –DNAse we should go for.
• In first week 90% of patients have depressed CH50 and C3 and normal C4.
39. IM:
• Garland pattern suggestive of large closely opposed granular deposits on
capillary walls have nephrotic range proteinuria.
• Starry sky have scatterd granular deposits have less severe disease.
• Mesangial pattern with predominant c3 staining,corresponds to resolving
phase.
• Staining with Ig G as well as c3 indicates active on going disease,only with c3
indicates a sign of on going reemission.
PATHOGENESIS;
• Implanted antigens leading to immune complex and complement
activation(alternate >classical )are most proposed ones.
• These imp antigens include Streptococcal pyogenic exotoxin B, Nephritis
associated plasmin receptor.
40.
41. TREATMENT:
• Supportive-Diuretics ,antibiotics,anti HTN,treatment of co morbidities
• Those presenting with crescentic GN and ARF too have very good recovery.
• Permanent renal failure occur in about 1% of children. Complete resolution
generally occur within 3-6 weeks of onset of nephritis.
• No evidence to date support that early treatment of
streptococcal disease either pharyngitis or cellulitis alter the
risk of PSGN
• Prognosis in elders is worse with high incidence of azotemia(up to
60%),nephrotic range proteinuria and ESRD.
43. • Rapid loss of renal function(Upto 50% decrease in GFR) with features
of glomerulonephritis accompanied by oliguria/anuria.(<3months)
• Histologically ,crescents must form in >50% of all glomeruli.
• Inciting event leads to focal rupture of capillary walls.
• MC cause –Immune complex mediated GN,and same in children.
• In adults-Paucimmune variety.
• Rarest –Anti GBM.
• Immuncomplex variety and Anti GBM variety we can 1/3rd to ¼ th
cases +ve ANCA too.
46. Immune complex mediated:
• Evidence of special inciting GN ,systemic immunecomplex disease leading to it.
• Idiopathic crescentic immune complex.
LM
• Along side of crescents in intact glomeruli we get varying combinations of capillary wall
thickening, endocapillary hypercellularity unlike in other two we get necrotizing
glomeruli,with total normal glomeruli in between,associated with sclerosis widespread.
• Crescents much less evident than in Anti GBM and pauciimmune ,so a/w good prognosis.
IM:
• Mesangial IgA deposits?
• C3 dominant deposists??
• Fine granular Ig G4 deposits??
• Coarse granular capillary wall thickening??
• ANA +immunecomplex?
• ANA + anti GBM??
47.
TREATMENT:
Influenced by the underlying etiology
Idiopathic variety we go for-Immunosupressive therapy with pulse
methylprednisolone 3-5 days, followed by 1 mg/kg prednisolone
tapered over 2nd and 3 rd month to alternate day regimen until
completely discontinued.Rituximab has also been beneficial in many
trials.
48. Anti GBM disesase:
Two peaks-young onset in male (2 nd -3rd decade)/second peak in female in 6th-7th
decade.
HLA-DR2
49. PATHOGENESIS:
• Ig G1(MC) antibody formed against NC/Collagenase resistant alpha 3
domain of type 4 collagen.(alpha 4-TMD,alpha 5-Alport syndrome, alpha 1-
paraneoplastic syndromes)
• Anti GBM antibodies(>95%) breech only the monomer subunits of
hexameric quaternary structures of Nc1 which are otherwise cryptic in
normal individuals, exposed by some environmental factors, genetic
susceptibility.
• ANCA association in about 30% cases.
MICROSCOPY:
• IM-Linear Ig G staining of GBM(diabetic glomerulosclerosis ,hypertensive
vascular disease,Fibrillary glomerulopathies???)
• LM-97% have some crescents,85% have more than 50% crescents
• Widespread necrotizing glomeruli with many crescents, sclerosis,
normal glomeruli in between.
50. C/F and prognosis:
• Picture of GN and associated with pul. hemorrhages that may be subtle or
lifethreatning,same BM material may be found in pulmonary capillaries-GOOD
PASTURE SYNDROME.
• Haemorrhages more common in smokers.
TREATMENT:
• Plasmapheresis(8-10timeneeded)+steroids+cyclophosphamide(3months
Rx)(i.v>oral??-less cumulative toxic dosage,less severe leucopenia)
• Patients who need dialysis becomes readily dialysis dependent.
• > 7 mg/dl creatinine with widespread glomerular and interstitial scarring,don’t get
benefit with immunosuppressive.
• If ANCA+ in same patients(cyclophosphamide is to be given )
• Once remission is achieved very rare relapse.
• Transplantation results are too good(Alport syndrome with alpha 3 antibody)-
Should wait for at least 6 months till serum antibodies are undetectable.
51. Paucimmune variety
C-ANCA
Antibody to proteinase 3(PR3)
Found in primary granules of
neutrophils and lysosomes of
monocytes.
This variety is associated with less
relapse. Although associated lung
and upper respiratory tract
involvement also signifies less
relapse.
Characteristically
GRANULOMATOSIS WITH
POLYANGITIS have 80-90%
positivity with it.
Association with patient exposed
to silica dust, alpha anti trypsin
deficiency.
P-ANCA
Antibody to MPO
Found in primary granules of
neutrophils and lysosomes of
monocytes
More relapse
Notable examples are MICROSCOPIC
POLYANGITIS and CHURG
STRAUSS SYNDROME.
52. Another pathogenic antibody being detected is lamp2 antibody.
Around 1/3 rd cases presents as isolated clinical manifestation of
kidney disease,although we can get pathological findings in many of
cases.
Rx:
Since mortality is very high in most of the cases,treatment is urgently
needed.
Induction therapy usually consists of plasmapheresis
,methylprednisolone and cyclophosphamide.
Steroids are tapered(up to 20 mg in 8weeks) soon after the acute
inflammation subsides and are maintained on cyclophosphamide or
azathioprine to prevent relapse for at least one yr.
Maintainence therapy is not needed in those who are dialysis
dependent and have no extra renal manifestations.
Benefit with MMF or Rituximab is controversial but recently most of
trials are supporting its use.IvIg have also been found beneficial in
some of refractory cases.
53. MESANGIO CAPILLARY GLOMERULONEPHRITIS
• Histological term,a rare GN .
• May be idiopathic ,more common being secondary
• Children 8-16yr most common,M=F
PATHOLOGY AND PATHOGENESIS:
• Type 1 –classical complement activation pathway mainly(Antigen???)
,generally associated with hepatitis C and autoimmune
disorders.{SECONDARY MOSTLY}
• Type2-Alternate pathway activation(c3NeF/absent factor H/antibody against
factor H-- leading to disinhibition of C3 convertase ie C3bBb)(DENSE
DEPOSIT DISEASE),associated with partial lipodystrophy syndrome.
• Type3-Like MGN subepithelial deposition, associated with complement
receptor deficiency.
• Type 2 and type 3 comes under another new category ie C3
glomerulopathies.
54. MICROSCOPY:
• Subendothelial dep. and mesangial hypercellularity are chief picture a/w
endocapillary thickening,global capillary wall thickening leading to picture of
HYPERSEGMENTATION AND LOBULATION.
• Tram track appearence on methanamine silver staining.
• IM staining is peripheral granular or band like complement specially c3(in type 2
and 3),Immunocomplex evident in type 1
55. C/F AND PROGNOSIS:
• May present as asymptomatic,nephritic and nephrotic poteinuria,acute
nephritic syndrome,ESRD(very high chance 50% in 10 yrs.)
• MPGN 2 a/w lipodystrophy,retinal pigmentation abnormlity.
Poor prognosis
HTN,impaired GFR,appearance of nephrotic syndrome,appearance of
crescents,MPGN 2 (more associated CRESCENTS)
LAB FEATURES:
Routine test for GN
Serum compliment levels-classical complement pathway (c1q,C4),alternate
pathway(c3)
Consistently depressed C3 alike PSGN in which C3 return to normal .
56. TREATMENT:
General treatment of GN
KDIGO guidelines - start of ACE inhibitor and Anti HTN drugs if
needed,in proteinuria>30mg/24hr
Specific treatment is needed (ie
steroids/immunosupressants/antiplatelets)when:
Proteinuria>3gm/24hr
Active interstitial or glomerular disease
Impaired renal function presentation
Progressive deterioration of renal functions
Some trials benefits the use of Dipyridamole, aspirin and warfarin
although not proven.
Post transplantation MPGN1 has been found to be of least recurrence
among primary GN but type 2 has maximum.
Eculizumab has been found to be of unproven benefit.