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GNA - Pengayaan Koass

Feb 20, 2018

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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

    7

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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

    21

    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)

    22

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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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