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Glomerular capillary membranes
mechanism of proteinuria
A SIZE-SPECIFIC BARRIER
A CHARGE-SPECIFIC BARRIER
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Glomerulonephritis
Synonyms: Glomerulonephropathy
Glomerular diseases
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e n on: A group of conditions in which inflammation in the
glomerulus occurs
The mechanisms for glomerular injury are complex
more often are inisiated by an immune response
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Classification of glomerulonephritis
1. Congenital or inherited:a. Alport syndrome
b. Congenital NS
c. Familial hematuria
.a. Primary or idiopathic:
b. Secondary:
1. infection-related2. associated with a multisystem disease
3. drugs
4. neoplasia
5. miscellaneous 6
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a. Primary or idiopathic:
Minimal changes
Mesangial proliferative GN
Membranoproliferative GN
Membranous glomerulonephropathy
IgA nephropathy Rapidly progressive GN
Focal proliferative GN
Diffuse proliferative GN proliferative GN
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b. Secondary:
1. Infection related: Poststreptococcal GN
Subacute bacterial endocarditis
Postpneumococcal GN
Shunt nephritis
Hepatitis B, C, HIV
Malaria, leprosy, schistosomiasis, etc
2. Associated with multisystem disease
Henoch-Schoenlein purpura Systemic lupus erythematosus
Hemolytic uremic syndrome
Collagen vascular disease: polyarteritis nodosa, vasculitis
Goodpasture syndrome, etc8
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b. Secondary.:
3. Drugs: Penicillamine, NSAID
Captopril, gold salts,
Trimethadione, lithium, mercury, etc
. Neo lasia
Leukemia
Lymphoma
Carcinoma
5. Miscellaneous
Renal transplant rejection
Sickle cell disease
Reflux nephropathy 9
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Classification of
glomerulopathies Clinical: primary x secondary
According time period: acute x subacute x chronic
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According renal biopsy: focal x segmental x diffuse
According number of cells:
non-proliferative x proliferative
According immunofluorescence:
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Glomerular Disease Primary glomerular disease:
Disorders in which the glomeruli are the sole or
predominant tissue involved. Usually these
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.
Secondary glomerular disease:
Glomerular injury is a feature of a systemicdisease, vascular, metabolic or genetic
disorders involving multiple organs or systems.
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Glomerulonephritis
- chronology -
acute: days to weeks
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subacute/rapidly progressive:
over weeks to few months
chronic: many months to years
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Glomerulonephritis
- location -
focal :
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Glomerulonephritis
- pathology -
proliferative: increased glomerular cell
intracapillary/endocapillary
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extracapillarycells in Bowmans space
crescent: half-moon-shaped collection ofcells in Bowmans space
often associated with rapidly progressive renal failure
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Glomerulonephritis
- pathology -
membranous:- expansion of glomerular basement membraneas a dominant feature
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- increased amount of homogenous non-fibrillarextracellular material (similar to GBM andmesangeal matrix)
fibrosis- deposition of type I and III collagen- commonly as a consequence of healing of
crescents or tubulointerstitial inf lammation
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Acute glomerulonephritis:
constellation of clinical manifestations caused by
glomerular injury and inflammation
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that leads to decline in glomerular filtration rate
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Etiology
Infections Bacteria: Streptococci, pneumococci, staphylococci,
Treponema pallidum, Salmonella typhi
Virus: Hepatitis B, Echovirus, Ebstein B virus, HIV.
Protozoa: Malaria
Vascular-colagen disease: urpura enoc c n e n, ,
Genetic Alports syndrome
Drugs Methicillin
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Symptoms and Signs
Hematuria (with RBC casts)
Proteinuria
Hypertension
Renal function im airment
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Oliguria
Elevated plasma creatinine/Reduction in GFR
Acute fluid overload Peripheral oedema
Pulmonary oedema
Congestive cardiac failure
Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3rd ed.,Oxford, Toronto, 2003,p.367-80.
Bagga A. Pediatric Nephrology, 6th ed.,Wlsevier, 2009,p.815-28
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Epidemiology
Actual incidence is not known, because the majorityof APSGN cases are sub clinical in nature
APSGN: schooll-aged children
5 15 years < 2 years : < 5%
Male > female
APSGN: skin infection younger than pharingeal infection
10-15% of nephritogenic infectionAPSGN
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Alatas A, et al. Maj Kedok Indones 1983Kazzi AA, et al.http://www.emedicine.com/emerg/topic219.htm. 2006
Parmar MS.http://www.emedicine.com/med/topic879.htm. 2006Smith JM, et al. Clinical paediatric nephrology. 2003
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Etiology Post infection of group A Streptococcus hemoliticus
Specific serotype of APSGN:
--
Type 49: skin infection (impetigo): onset: 21 days ( 3-6 weeks)
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Nephritogenic strains of Streptococci
Group ABeta-hemolytic
Respiratory tract M 1,2,4,12,18,25
Skin M 49, 55, 57, 60
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Group CStreptococci
Streptococcus zooepidermicus
Site of infection:upper respiratory tract: pharynx, tonsilles, middle earskin
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C5a peptidase
Protein T
Protein F
Protein M
Eksotoksinpirogenik
Streptolisin S
Streptolisin OHialuronidase
Streptokinase
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M-like protein
Kapsul asam
hialuronat
Dinding sel:
Peptidoglikan,
polisakarida grup A
Membran sel
Plasminogen-binding site
Figure. Schematic diagram ofStreptococcus pyogenes
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Tonsilopharingitis
Scarlet fever
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Fasciitis
nec
rotizing
Impetigo
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a. Host factors: Age 5 -15 years
Sex : boys > girls Genetic Nutrition
Socio-economic conditions
b. Bacterial factors: MProtein
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n os rep oz ne Cationic protein) Streptococcal pyrogenic exotoxin B Nephritis associated plasmin receptor Streptokinase Streptolysin O Streptodornase Hyaluronidase acid Neuraminidase DNA-ase
Nicotinamide adenine dinucleotidase
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Pathogenesis
Hypothesis:
Circulating immune complex formation
In situ immune complex formation
Autoimmune processeuram n ase pro uce y s rep ococc removes s a c ac rom
Ig, alters endogenous IgG and makes it autoantigenic
altered IgG form circulating complexes
deposited inkidney
Streptokinase:Plasminogen plasmin
Activate complement casacade
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Clinical manifestations
5 - 15 years
After pharingytis or impetigo:
-pharingytis: 7-14 days
-skin infection: 3-6 weeks
Acute nephritic syndrome:
Hematuria
Oedema
Hypertension : headache, seizures, vision abnormality
Proteinuria
Oliguria/anuria
29Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79
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Fluid overload
generalized oedema: 85% acute pulmonary oedema: 14%
heart failure: 2%
Hematuria:
microscopic: + 100%
macroscopic
Hypertension: 60-80%: encephalopathy hypertension: rare
Nephrotic proteinuria: < 5%
Hypoalbuminemia: mild, intravascular dilution AnaemiaAnaemia
GFR: 45%
Normal: 1-2 weeks
30Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3rd ed., Oxford, 2003;h.3-79
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Laboratory
Urinalysis: Hematuria
Proteinuria
Erythrocyte casts
Leucocyturia
Leucocyte casts
Dysmorphic erythrocyte
Normal
Streptococcus infections: Antibody for streptococcus antigen :
Titer ASO: pharingytis (80-90%),
skin infection (
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Laboratory
Immunology: Complement:
C3 C4 normal
renal function: Creatinine and ureum
Hyperkalemia Hyperphosphatemia Acidosis Calcium and phosphate
Hematology: Mild anemia Mild thrombositopenia
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Smith JM, Faizan MK, Eddy AA. Clinical Pediatric Nephrology, 3 rd ed., Oxford, 2003;h.3-79
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Complications
Encephalopathy hypertension
Acute renal failure
Congestive heart failure
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Treatment
1. Bed rest2. Antibiotic for eradicating streptococci
- Penicillin 10 days- Erythromicyn
3. Dietetic fluid & salt restriction
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- low protein 1 g/kgBW/day- low salt 1 g/day- IVFD as necesarry
4. Prolonged anuria
dialysis- peritoneal dialysis- haemodialysis
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Treatment ..
5. DiureticsFurosemide 1 mg/kgbw/dose 2x/ day
6. Symptomatic treatment
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hypertensive encephalopathycongestive heart failureacute renal failure
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Indications for in-patient management
of APSGN
Hypertension
Oedema
Macroscopic hematuria
Elevated plasma creatinine
Electrolyte abnormalities
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Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3rd ed.,Oxford, Toronto, 2003,p.367-80.
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Prognosis
95 98% : complete resolution
: self limited disease
: 1 2 weeks
< 3% : died in the acute phase< 1 :
Hematuria-proteinuria until 12 months: CGN
Ad vitam/for life : good
Ad sanationum/for cure : good
Ad fungsionum/for function : good
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Clinical course of APSGN symptoms
Oedema : subside day 3 (4,3 + 1,8)
Macroscopic hematuria : subside day 2 (5,1 + 4,2)
Hypertension : subside day 3 (4,6 + 2,4)
Oliguria : subside day 3 (3,8 + 2,6)
C3 complement normal : 6-8 weeks
ASO normal : 1-6 months
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Gross haematuria,
Oliguria, azotaemia
Hypertension
Depression of C3
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2 weeks 4 weeks 2 months 6 months 1 year 2 years
ers s en pro e nur a
Microscopic haematuria
or intermittent
Orthostatic proteinuria
Fig. Natural history of APSGN
Smith JM, Faizan MK, Addy AA. Clinical Paediatric Nephrology, 3rd ed.,Oxford, Toronto, 2003,p.367-80.
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Acute non post streptococcal GN symptoms are not similar with APSGN
family history of glomerular disease
under 4 years or over 15 years previous history of similar symptoms
evidence of extra-renal disease
evidence of acute or chronic non streptococcalinfection
evidence of chronic renal disease
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Shunt nephritis
4% of infected shunt
Hydrocephalus with VP shunt
Coagulase-negative Staphylococcus
Fever, lethargy, arthralgia, hepatomegali, purpura, adenopathy, BW
,
Kidney: hematuria, proteinuria (30% nephrotic), azotemia,
hypertension
Lab: anemia,lecocytosis, ESR, C3 dan C4 (90%)
Therapy: - AB
- removal shunt
- supportive
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Infective endocarditis - nephritis
Rare
Staphylococcus aureus
Renal manifestations:
Proteinuria
Hypertension
Renal function
GSFS, diffuse proliferative GN, rapid progressive GN
Hypocomplementemia: 60-90%
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Hepatitis C - nephritis
MPGN, acite proliferative GN, mebranousnephropathy
Rare
proteinuria
renal function
C3 and C4
Therapy:
Antiviral: ribavarine
-interferon: proteinuria
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HIV Nephritis
Urinalysis: routine
FSGS, minimal changes, IgA nephropathy
Renal manifestations:
Proteinuria nephrotic
Hematuria: not significant
Normotension
Hypocomplementemia
Therapy: antiviral
ACE inhibitor: proteinuric effect
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Others glomerulonephritis
Henoch Schoenlein purpura nephritis
Membranoproliferative glomerulonephritis
Lupus nephritis
ANCA positive nephritis
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APSGN Henoch-SchnleinPurpura
IgANephropathy
MPGN SLE ANCA-positivevasculitis
Mean age
(years)
Antecedent
infection
Gross
haematuria
5-15
Yes
30%
5%
4-14
35%
20%
5-10%
10-20
Concurrent
common
50-80%
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Pathogenesis .
Antibodies elicited by nephritogenic streptococci cross react
with renal antigens leading to antibody mediated glomerular
damage Immune complexes consisting of Streptococ antigen and
antibodies are trapped in the glomeruli
The complement cascade is activated resulting in increased
glomerular celluarity
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Acute inflammatory response in the glomeruli attract
polymorphonuclear leucocytes
Endothelial cells swell, fibrin is deposited, and the lumen of
capillaries are thereby occluded Release of proteolytic enzymes from polymorphs disrupts the
integrity of the glomerular basement membrane and allows the
excessive escape of blood cells and plasma constituents in the
urine
Leads to decreased GFR and oliguria
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