GNA - Pengayaan Koass

7/24/2019 GNA - Pengayaan Koass

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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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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



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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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