Glomerular diseases are a heterogeneous group of kidney disorders that can be primary, secondary, or hereditary in nature. They involve pathological changes to the glomeruli, such as injury to the mesangial cells, endothelial cells, basement membrane, or podocytes. This can lead to clinical manifestations like proteinuria, hematuria, edema, hypertension, and renal failure. The mechanisms of glomerular injury are complex, often involving the immune system through immune complex deposition, complement activation, or cytotoxic antibodies. Glomerular diseases have diverse clinical presentations and outcomes depending on the specific cause and severity of involvement.
Membranous GN
MOST COMMON cause is idiopathic (85%); peak age 30-50; male:female, 2:1
May be secondary to:
Drugs-captopril, penicillamine, gold, mercury, trimethadione, NSAIDS
Infections-malaria (P. malariae), leprosy, schistosomiasis, syphilis, hepatitis B and C, filariasis, hydatid disease and enterococcal endocarditis
Diseases-malignancy (Carcinoma of breast, lung, colon, stomach, and esophagus) melanoma, renal cell CA, SLE, sarcoidosis, diabetes, thyroiditis, sickle cell anemia, Crohn’s disease
Membranous GN
MOST COMMON cause is idiopathic (85%); peak age 30-50; male:female, 2:1
May be secondary to:
Drugs-captopril, penicillamine, gold, mercury, trimethadione, NSAIDS
Infections-malaria (P. malariae), leprosy, schistosomiasis, syphilis, hepatitis B and C, filariasis, hydatid disease and enterococcal endocarditis
Diseases-malignancy (Carcinoma of breast, lung, colon, stomach, and esophagus) melanoma, renal cell CA, SLE, sarcoidosis, diabetes, thyroiditis, sickle cell anemia, Crohn’s disease
This is about glomerulonephritis and all that you need to know. It contains different images illustrating this subject matter, well defined outline, different aspect of glomerulonephritis, which include acute and chronic glomerulonephritis, nephritic and nephrotic syndrome, investigations, how to diagnose glomerulonephritis, treatment and important discussions on Glomerulonephritidis. It is a presentation you need to check out.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
This is about glomerulonephritis and all that you need to know. It contains different images illustrating this subject matter, well defined outline, different aspect of glomerulonephritis, which include acute and chronic glomerulonephritis, nephritic and nephrotic syndrome, investigations, how to diagnose glomerulonephritis, treatment and important discussions on Glomerulonephritidis. It is a presentation you need to check out.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
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
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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.
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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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.
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.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
2. Glomerular diseases (glomerulopathy)
heterogeneous group of diseases
Dividing:
a) Primary glomerulopathy
b) Secondary glomerulopathy
c) Hereditary glomerulopathy
– can be manifestation of systemic diseases, vascular, metabolic or
genetic disorders affecting also other organs
The mechanisms for glomerular injury are complex
more often are iniciated by an immune response
exclude
3. • A group of diseases:
pathological changes:glomerular
injury
clinical manifestation:protenuria/
hematuria
complicated causes/mechanisms
various clinical manifestation
different prognosis
multiple treatment
4. What kind of nephritis does Alport syndrome belong to?
1 Primary glomerular diseases
2 Secondary glomerular diseases
3 Hereditary glomerular diseases
5. Drugs and poisons product of metabolism
Special capillary bulb structure
The renal blood supply is abundant
Vasculitis
6. Clinical manifestation of GN
initiation hematuria proteinuria Edema,hyp
ertention
Renal
failure
Acute GN acute 100% 100% frequent resumable
rapid
progressive
GN
acute 100% 100% frequent ARF
Chronic GN latent frequent frequent frequent CRF
Latent GN latent frequent <1g/d - -
Nephrotic syntrome
9. Immunopathologic mechanisms
Damage of kidney depend on:
- mechanism and intensity of immune reaction
- collocation of antigens (Ag)
Mechanisms:
Damage by immunocomplexes
Damage by cytotoxic antibodies (Ab)
Cell-mediated immune injury = delayed-type
hypersensitivity
Damage by complement and proinflammatory mediators
10. Cytotoxic (Type II) reaction
– antibody mediated cytotoxicity (ADCC)
These occur when antibodies interact
with antigens found on cell
surface
2 mechanisms of cytotoxicity:
1. Ab mediate cell destruction
via mechanism ADCC (cell
cytotoxicity dependent on Ab)
2. Ab directed against cell-
surface antigens mediate cell
destruction via complement
activation
11. Type III reaction – immune complex-
mediated hypersensitivity
- The reaction of antibody with
antigen generates immune
complexes. In some cases, large
amounts of immune complexes can
lead to tissue damage
They deposited in various
tissues
induce complement activation
and ensuing inflammatory response
Antigens can be:
a) Endogenous – for example DNA in
SLE
b) Exogenous – bacteria, viral,
parasitical Ag
12. The magnitude of the reaction depends on the quantitity of immune
complexes as well as distribution within the wall of glomerular capillary
14. Delayed – type hypersensitivity (Type IV)
T lymphocytes may also recognize
antigen
When they do, a mononuclear cell
infiltrate may accumulate at the
site of Ag concentration and
lead to the elaboration of toxic
products and tissue injury
18. Why does IC deposit in the glomeruli
• Large area of glomurular capallaries
More chances of contact
• Net structure of CIC
Easy to deposit and settle down
• Decrease clearance of CIC
clearance dysfunction of mesangial cells
Disability of mononuclear macrophage
Component or function defect of complements
19. Balance of deposit and clearance of IC
determines thd situation of the diseases
• Persistence of antigen
• Clearance dysfunction of mesangial cells
• Disability of mononuclear macrophage
• Component or function defect of
complements
IC deposit>clearance
20. • Non immune mechanisms
Glomerular hypertension
Hyperlipidemia(LDL-Cho)
Advanced glycosylation end products
protein
glomerulosclerosis
21. inflammation
• Mediators of inflammation
A group of molecules which act as mediators of
inflammation and complicated biological function
• Original mediators in kidney
Extrinsic cells in kidney
Infiltrative neutrophil,lymphocyte,mononuclear
macrophage,platelet
intrinsic cells in kidney
Mesangial cells,tubular cells,endothelial cells
22. Mediators of inflammation
• Active oxygen and active nitrogen
• Lipids
• Complements
• Cytokines
• Adhension molecules
• Growth factors
• Vasoactive substances
23. Effects of inflammation
mediators
• To arouse or promote
Proliferation of cells
Accumulation of extracellular matrix
Changes of histological structure
Expression of immunomodulating
molecules and adhension molecules
24. Mechanism of primary GN
Immune
Mesangial cells,tubular
cells,endothelial cells
Essential in the initiation
Essential in the progressive period
inflammation
Inflammation cells
Extrinsic cells Intrinsic cells
Infiltrative
neutrophil,lymphocyte,mononucl
ear macrophage,platelet
Inflammation mediators
Active oxygen and active nitrogen,cytokines,growth factors,chemotatic factors,
complments,vasoactive subtances,coagulation and fibrolysis system,enzyme
Glomerular injuries
Non immune
26. Pathogenesis
Normal glomerular structure
• Glomerular tuft composed 4 major components
– Endothelial cells
– Visceral epithelial cells or Podocytes
– Mesangium
– Capillary loop basementmembrane
• Capillary wall
– carries a net negative charge
– acts as both
– charge-selective
– size-selective filter
27. Glomerular capillary wall:
Size selective filter
The capillary wall restricts the passage of large molecules into Bowman's space, while
there is less restriction of smaller molecules.
As radii increase, filtration decreases, approaching zero at radii > 4.2 nm
28. Glomerular capillary wall:
Charge-Selective Filter
The capillary wall restricts the passage of negatively charged molecules such as albumin
while neutral substances pass more freely and are restricted by size from passing into
Bowman's space.
29. Pathological changes
• LM
Mesangial cells,matrix of mesangium
Endothelial cells
Epithelial cells
Basement membrane
Loops of glomeruli
• EM(Electron microscope)
• Foot process
Basement membrane
Hyperplasy of mesangium(electron dense deposits)
• IF
Sites,appearances,type of deposits(IG or C)
31. Extents of injury
• Primary GN:glomerular injury-only or dominating
injury
• Secondary GN: glomerular injury-a part of systematic
diseases
• Diffuse:impaired glomeruli>50%
• Focal: impaired glomeruli>50%
• Global:impaired capillary loops of a glomerule>50%
• Segmental:impaired capillary loops of a
glomerule<50%
32. Pathological types of primary
GN
• Minimal change of glomerulonephritis
• Focal segmental lesions
• Diffuse glomerulonephritis
• Unclassified glomerulonephritis
33. Minimal Change Disease (MCD)
• Most common cause of nephrotic syndrome in childhood
– In a prospective study of untreated children with N.S.:
• minimal change disease was found in 76.6%.
• Only 10% to 30% of adult cases of nephrotic syndrome
– Percentages vary in different parts of the world
• The clinical onset of nephrotic syndrome associated with:
– upper respiratory infection
– with routine prophylactic immunizations
– Other genetic and environmental factors may also be
important
34. Morphologic Features (LM & IF)
• LM: normal in glomeruli, tubules and interstitium
• IF: No immune deposits
35. • diffuse effacement of the epithelial cell (podocyte) foot processes
Morphologic Features (EM)
36. Clinical Course
• Most patients with MCD develop mild periorbital edema as
initial complaint
• Proteinuria: to be "selective“
– primarily of albumin
– Microscopic hematuria is rare (13 to 36%)
– Hypertension: also unusual
• Treatment:
– Most patients (90%) respond to an 8 week course of steroids
– Cytotoxic agents: may be used in steroid resistant cases (~10%)
– Renal failure: rare
– Relapses are common
37. Focal Segmental Glomerulosclerosis
(FSGS)
(a ) often present with severe proteinuria
(b ) 30-50% combine with hypertension
(c ) HIV may associated with FSGS
(d ) subepithelial “ hump” of glomuerulus in
electron microscopy
38. Focal Segmental Glomerulosclerosis
(FSGS)
• Prevalence in idiopathic nephrotic syndrome :
– 10% of childhood
– 15-20% of cases of adult
• Symptoms and signs: common with
– proteinuria
– microscopic hematuria
– Hypertension
• Pathogenesis:
– sclerosing lesions and their progressive nature are debated
• hyperfiltration,
• increased intracapillary glomerular pressure
39. Morphologic Features
• LM: focal and segmental glomerular sclerosis with capillary loop collapse, hyaline and
lipid deposition and often adhesion to Bowman's capsule
– The remainder of the glomerular tuft is normal in appearance; thus the term 'segmental'.
The lesions are considered to begin or to be more common near the corticomedullary
junction.
• IF: Deposition of IgM and C3 in the mesangium or in the areas of segmental sclerosis
may be seen, but no immune complex deposition is present.
• EM: effacement of podocyte foot processes. Podocyte denudation may be present
focally as an early lesion, and segmental sclerosis may also be seen
40. Clinical Course
• FSGS may be :
– primary (idiopathic)
– secondary to a number of etiologic agent :
• Unilateral renal agenesis
• Renal ablation
• Sickle cell disease
• Morbid obesity (with or without sleep apnea)
• Congenital cyanotic heart disease
• Heroin nephropathy
• HIV nephropathy
• Aging kidney
41. Membranous Glomerulonephritis(MGN)
• Antibody mediated disease
– ICs localize to subepithelial of the capillary
loop
• between outer aspect of GBM and podocyte
• Immune complexes
– develop in situ
– deposition of circulating ICs (less likely)
– antibody may bind to
• intrinsic glomerular antigen
• exogenous antigen planted on the capillary wall
– Serum complement level was normal
42. Clinical Manifestation
• more common in adults (peak 40-50 y/o)
• mostly older than 30 years at diagnosis
• 35-50% of cases of adult nephrotic
syndrome
• Most patients present with:
– heavy proteinuria: most commonly in nephrotic
range
– insidious in onset
– few patients accompanying microscopic
hematuria
43. Morphologic Features
Capillary walls are thickened and numerous subepithelial "spikes" are
present on capillaries of this glomerulus, representing elaboration of
basement membrane between subepithelial immune deposits.
LM
46. Membranoproliferative Glomerulonephritis
(MPGN) (mesangiocapillary glomerulonephritis)
• Chronic progressive glomerulonephritis
– occurs in older children and adults
• Circulating immune complexes (CIC)
have been identified in 50% of patients
• activation of the complement system
with hypocomplementemia, is a
hallmark of MPGN.
47. MPGN (IF)
Type I: subendothelial and mesangial deposits of IgG and C3
48. MPGN (EM)
Electron microscopy
Electron microscopy
Type I: deposits in subendothelial and mesangial
Duplication of the capillary loop basement membrane between the
deposits and interposed mesangium, and the endothelial cells.
50. In summary
• Proliferation of mesangium can presents in various
types of GN
• Proliferation and subsequent stiffness of mesangium
may be the results of various types of GN
• FSGS:primary—later phase of the disease itself
secondary—later phase of other type of GN
• Crescents can presents in different types of GN
54. RBC from glomeruli
Squeezing through
GBM
Changing when passing tubule
with different osmosis
Dismorphic RBC
Phase contrast
microscopy
Dismorphic
RBC>50%,hypothesis
of glomerular bleeding
Dismorphic
RBC>50%,final
diagnosis of
glomerular bleeding
Urinary RBC volume distribution curve
Dissymmetry curve
MCV of urinary
RBC<that in blood
55. edema
Glomerular diseases
GFR↓
Intrinsic RAS or
aldosterone↑
Water sodium filtration↓
Water sodium readsorpation↑
Primary Water and sodium
retention
Effective circulation
blood volumn↑
edma
Effective circulation blood volumn↓
Large ammount of
urinaryprotein lost
hypoalbuminemia
Colloid osmotic
pressure↓
secondary water and
sodium retention
56. hypertention
Glomerular diseases
Primary Water and sodium
retention
Volumn dependent
hypertension
Stimulus,such as ischemia
Vessoconstrictive
substances↑ RAS ALD
Vessoactive substances
dependent
Vessodilatory
substances↓ PGI2,PGE2
57. Clinical types of GN
• Glomerulonephropathy
Confined concept
Leading manifestation: proteinuria /hematuria
Extensive concept
Glomerular diseases
• Glomerulonephritis
Leading manifestation:hematuria /proteinuria
58. Clinical manifestation of GN
initiation hematuria proteinuria Edema,hyp
ertention
Renal
failure
Acute GN acute 100% 100% frequent resumable
rapid
progressive
GN
acute 100% 100% frequent ARF
Chronic GN latent frequent frequent frequent CRF
Latent GN latent frequent <1g/d - -
60. Pathological changes
• Endocapillary proliferative GN
Acute phase
Proliferation of endothelial
/mesangium
Recovery phase
Only mesangium
proliferation,sometimes minor injure
63. Laboratory finding
• Acute phase of infection of strep.
Elevated ASO titer
Only the marker of infection,not
nephritis
• Acute phase of immune reaction
Serum C3/total complement↓,return
normal within 8w
Blood CIC↑
64. Natural history
• Edema and hypertention
Disappear in one month
• Hematuria,proteinuria
Usually reduce in one month,resolve in2-
3 months
Some resolve in 6-8 months
• C3:return to normal in two months
66. Indications of renal biopsy
• Oligouria>1w,except
ECBV,insufficient,urinary tract
obstruction,etc
• Progressive renal failure
Unresolved in 2 months
Untypical manifestation,or with NS
67. treatment
• Supportive treatment
• Rest
• Food and water
• Restrictive intake of NaCL<5g/d
If moderate to severe edema or hypertention
• Water
If decreased urine volumn
• Protein
Renal failure,but not dialysis yet
68. Treatment of infection
• Penicilin for 2w
• Tonsillectomy if recurrent attacks of tonsillitis
• Patient is stable:U pro<1g/d,Urbc<10/HP
• Penicilin for 2w before and after the surgery
• Symptomatic treatment
Diuresis
Antihypertention
dialysis
70. Rapidly progressive glumerulonephritis
• Rapidly progressive glumerulonephritis
syndrome
• Some induced by respiratory infection
• Acute onset,rapidly progressive
• Renal failure within a few weeks to a few
months
71. • Primary RPGN:crescentic GN
• Other primary GN:other pathological
changes with lots of crescents
• Secondary RPGN:SLE,SHP,etc
72. Type 1
Anti GBM
Type 2
IC
Type 3
Pauci-immune
Linear GBM
deposits
Granular
GBM/mesangium
deposits
-
Anti-GBM+ C3↓CIC↑ 70-80%small
vessel ANCA+
The
young/middle
aged
The middle
aged/aged
The middle
aged/aged
73. diagnosis
• Acute onset
• Rapidly progressive
• Renal failure within a few weeks to a few
months
• Acute renal failure-chronic renal failure
74. Treatment-early!!!
• Aim to humoral immune mechanism
• Plasmapheresis discard the antibodies
plasm exchange immoadsorption,type1
typ2
• Drugs:glucocorticoid+cytotoxic drugs
MP05.-1.0g/d,repeat if necessary
CTX
type2-type3
75. Symptomatic treatment
• Renal failure
Balance of fluid,electrolytes and acid
base
Dialysis
• Infection
• hypertension
80. Point of diagnosis
• Chronic onset
• proteinuria and/or hematuria
• Protracted and progressive
81. AGN CGN
age children Young/middle-aged
Preliminary
infection
frequently sometimes
Latent period 1-3w <1w
onset acute Chronic,insidious
hematuria 100% Sometimes no
edema frequently Sometimes no
hypertension frequently Sometimes no
ASO frequently↑ normal
Blood C3 ↓,<8W persistent↓/normal
prognosis <1y protracted and
83. Treatment
• Target Inhibit immune reaction
Halt the progression of disease
• Restrictive intake of protein
<0.5-0.8g/kg/d
Protein of high biological value
↓Pressure in glomeruli
84. antihypertention
• Less than 140/90mmHg
Ideal target125/83mmHg
• ACEI/ARB:dialation of efferent glomerular
Arteriole>dialation fo afferent
Pressure in glomeruli↓
Upro↓
Postpone glomerulosclerosis
86. Four major pathogenetic forms of glomerular
injury
In non-proliferative glomerulopathy:
Damage by antibodies
Damage mediate by complement
In proliferative glomerulopathy:
Damage by circulating proinflammatory cells (especially
neutrophils and macrophages)
Damage by localy activating resident cells (for example
mesangial cells)
87. Classification of glomerulopathies
• Clinical: primary x secondary
• According time period: acute x subacute x chronic
• According renal biopsy: focal x segmental x diffuse
• According number of cells: non-proliferative x
proliferative
• According imunofluorescence:
90. Histologic pattern
• May not correlate with
the clinical presentation
• Various histological
types of
glomerulonephritis
91. B: “Minimal changes” GN = lipoid nephrosis: some mesangial proliferation,
edematous podocytes, fusion (“loss”) of their foot processes
C: Intracapillary mesangial proliferative GN: proliferation of endothelia and
mesangium, peeling off of enthelial cells from the GBM, duplication of GBM,
“humps” formed by immunocomplexes
D: Crescentic GN: proliferation of all components (aggressive white cells, endo-
and epithelia, mesangium, epitheloid and giant cells), leakage of fibrin.
Hypersensitivity reaction type II or IV
E: Membranous GN: Precipitation of immunoglobulins on the outer surface of the
GBM (“spikes” complete incorporation of Ig into the membrane)
F: Proliferative sclerotizing GN: advanced mesangial proliferation narrowing
and destruction of capillaries
92. Acute glomerulonephritis (poststreptococcal
GN)
Is commonly caused by infection by certain
strains of group A beta-hemolytic
Streptococci (pharyngitis, pyoderma)
Ab against streptococci react with vimentin
imunokomplexes
nephritis develop after a latent period of
about 2-3 weeks
Clinical syndrome: nephritic syndrom
Histologic pattern: intracapillary
proliferation of mesangial and endothelial
cells with subepithelial („humps“) and
subendothelial deposits (C3, or IgG)
Acute diffuse proliferative GN
93.
94. Postinfectional non-streptococcus
glomerulonephritis
Acute glomerulonephritis can develope also in the course of other infections:
- stafylococci - herpes virus
- pneumococci - EBV
- Klebsiella pneumonie - virus hepatitis B
GN in infection endocarditis
GN in visceral abscessus (especially lung)
Histologic pattern and clinical syndrome – similar one as in poststreptococcal GN
95. Focal proliferative glomerulonephritis
- different etiology:
IgA nefropathy
Nephritis in systemic lupus erythematodes (SLE)
Nephritis in bacterial endocarditis
Henoch-Schölein purpura
96. Rapidly progressive glomerulonephritis
(RPGN)
Heterogeneous group of diseases, it is characterised by intense proliferation
of glomerular/capsular epithelial cells in the form of a crescent.
crescemt = accumulation and proliferation of extracapillary cells.
The glomerular capillaries collapse and are bloodless, and fibrin can be
identified within the capsule
it can stimulate proliferation of parietal epithelial cells
deposits of fibrin compress the glomerula capillaries tuft
( GFR and destruction of glomerulus)
97. Three forms of RPGN
GN with creation of antiobdies (IgG, IgA) agains
GBM (anti-GBM)
- linear deposits of Ig
(+ alveolocapillary BM) Goodpastures´ syndrome
GN with granular deposits of Ig and complemen
- formation of crescent is complication less serious
intracapillary proliferative GN (IgA nefropathy, SLE,
acute GN e.g.)
GN with ANCA antibodies
- ANCA ab (Ab agains cytoplasma of neutrophiles)
2 forms – systemic disorders
(Wegener granulomatosis)
- only renal disease
Crescent GN
98. Goodpastures´ syndrome
It is charecterised antibodies against basal membrane of glomeruli
(alveolocapillary membrane)
Etiology: combination of exogenous factors (smoking, infection, toxines)
with genetic predisposition (HLA B7, DR2)
Pathogenesis: GBM is composed by collagen IV with proteins
(laminine, entaktine, tenascine) and proteoglycans
Goodpastures antigen
(localised in C-terminal non-collagen globular
domain (NC1) of the molecule 3 chain of collagen IV
formation of Ab (IgG1 – can activate complement)
damage of BM
Clinical manifestation: typically presents with crescentic glomerulonephritis
+ pulmonary hemorrhage
99. Slowly progressive glomerulonephritis
Group of GN called membrane-proliferative GN
2 forms:
in 1 form : - levels of complements in plasma
- subendothelial and mesangial deposits are present
findings: proteinuria or picture of nephrotic syndrom
in 2 form: - activation of complement is due to nephritic factor C3
- intramembranous deposits are present
findings: proteinuria or picture of nephritic syndrom (similary as in
RPGN)
101. „Minimal changes“ GN (lipoid nephrosis)
Especially in children
Pathogenesis ambiguous – connection with
viral infections, vaccination, atopy,
application some drugs (antiphlogistics etc.),
Association with several HLA antigens (DRw7,
B8, B12 …)
Finding: loss of negative charge
( permeability for some proteins –
albumins)
Histologic pattern: fusion („loss“) of foot
processes of podocytes (pedicules), edematous
podocytes, some mesangial proliferation
Therapy: corticoids
102.
103. Focal (segmental) glomerulosclerosis
More serious degree
- focal: < 50% glomeruli are affected
- diffuse: > 50% glomerulů are affected
- segmental: only a part of the glomerular tuft is
involved
- glomerulosclerosis: obliteration of capillary
lumens
104. Membranous GN
• Diffuse thickness of GBM due to deposition
of IK in basement membrane
• Strong association with HLA (B8, DR3) and
genes of alternative way of activation of
complements (Bf)
• Often secondary etiology:
- drugs (Au, penicilamin…)
- tumors (especially ca GIT)
- infection (hepatitis B)
• Clinical manifestation: nephrotic syndrome
with mikroscopic hematuria and sometimes
hypertension
• Therapy: according etiology
107. Membranoproliferative (mesangiocapillary)
glomerulopathy
- Is characterised by hypercellularity of the glomerular cells and basement
membrane thickening
- 2 forms: classical form – proliferation of mesangial matrix with expansion to
capillary walls between endothelium and BM
disease of dension deposits – non-linear accumulation of material in
lamina densa of the basal membrane
- etiopathogenesis: ??? - association with infection (endocarditis, abscessus….)
- genetic faktors (HLA B8, DR3…)
- Clinical syndrome: nephrotic proteinuria with microhematuria, hypertension,
anemia and decreased levels of the complements (C3)
108. IgA nephropathy (Berger´s disease)
• Mesangioproliferative GN with deposits of IgA, event. C3
• Etiology: - unknown, clinical manifestation is associated with infection –
with latent period 2-3 days
- association with HLA (DQ, DP)
T-lymphocytes produce levels of IL-2 (+ IR-2R) and they
are constantly stimulate
production of IgA by B-lymphocytes
• Clinical manifestations: asymptomatic hematuria - nephrotic syndrome
109. Chronic glomerulonephritis
Common terminal result of many glomerular
diseases
(„end stage kidney“)
It is charecterised by different degrees of
sclerotization and proliferation
Pathogenesis: damage (loss) of nephrons
hyperperfusion
hyperfiltration
sclerosis of glomeruli
110. Glomerulopathy in connective tissue disorders
SLE predominantly affects women, who account for 90% cases
The age of onset is usually between 20 and 40 years
Many different tissues and organs may be involved (the body produces
antibody against its own DNA), but renal involvement is the most
significant in terms of outcome
Histologic pattern:
WHO classification – normal glomerules (typ I)
- mezangial GN (typ II)
- focal proliferative GN (typ III)
- diffuse proliferative GF (typ IV)
- membranous GN (typ V)
- glomerular sclerosis (typ VI)
Systemic lupus erythematosis
111. Vasculitis
Heterogenous group of diseases characterised
by necrotizing inflammation of vessels
Etiology: primary x secondary
Pathogenesis:
- damage by immunocomplexes
- ANCA (pauciimmune form)
- damage by cells (IV. typ)
112. Henoch-Schönlein purpura
- systemic vasculitis affecting medium-sized vessels
especially in children and younger people
It is frequently develops post-infections
Clinical manifestation: - non-trombocytopenic purpura
- affect joints, serose membrane, GIT and
glomeruli
alterations are similar to finding in IgA nephropathy
113. Polyarteritis nodosa
- is an inflammatory and necrotizing disease involving the
medium-sized and small arteries throughout the body.
- Men are more commonly affected than women
Etiopathogenesis: usually unknown
Clinical manifestation: variable – general symptoms +
specific symptoms
(skin, kidney, GIT, heart…)
Histologic pattern: focal glomerular sclerosis, crescents
114. Pauci-immune necrotizing GN
Wegener´s granulomatosis
- is a vasculitis leading to sinus, pulmonary and renal disease
glomerulonephritis
90% of such patients have a positive ANCA
ANCA – react with neutrophils
respiratory burst of phagocytic cells
release of free radicals
degranulation
injury to endothelial cells
115. Diabetic nephropathy
= diabetic intracapillary glomerulosclerosis (sy Kimmelstielův-Wilsonův)
Etiopathogenesis: hyperglycemia affects conformation BM and mesangial matrix
renal flow and glomerular pressure
(hyperfiltration)
proliferation of cells
thickness GMB with expansion of mesangia
glomerulosclerosis
Clinical manifestation: latent stage - asymptomatic
incipient stage
manifest stage of diabetic nepropathy
chronic renal failure
117. Amyloidosis
Kidney belong to organs most frequently affected by amyloidosis
AL amyloidosis – is a complication of myeloproliferative diseases (myelom,
(primary) makroglobulinémie)
AA amyloidosis – is a complication of chronic inflammatory diseases (RA,
(secondary) TBC, Crohn´s disease e.g.)
Clinical manifestation: nephrotic syndrom, subsequently renal failure
develops
118. Hereditary nephropaties
Alport syndrom
- Hereditar nephritis with deafness (X chromosome)
- Pathogenesis: congenital defect of collag synthesis
GMB very slight or with more layers
GN focal (diffuse) proliferation with segmental sclerosis
hematuria, proteinuria or renal failure (males)
Congenital nephotic syndrom
- AR heredity
- Pathogenesis: defect of syntesis of basal membrane
- pronounced and non-selective proteinuria
Nephrotic syndrom from first weeks of the life --- renal failure