Professional Documents
Culture Documents
08 Glomerulo-Kuliah
08 Glomerulo-Kuliah
Lestariningsih
Glomerulonephritis
1. Bowman space
2. Bowman capsule with epithelial
cells (parietal epithelial cells)
3. Podocytes, foot processes
(visceral epithelial cells)
4. Endothelial cells (yellow)
5. Mesangial matrix (blue)
6. Mesangial cells (red)
7. Macula densa
8. Afferen artery
9. Efferen artery
10.Distal convuluted tubule
Glomerulus
Matriks ekstraseluler
NOMENCLATURE
• Clinical Presentation
• Chronic glomerular inflammation: proteinuria,
hematuria, hypertension, variable effect on GF.
• Pathology Findings
• Proliferation of mesangial cells and matrix
• Etiologies
• Early and milder forms of most diseas causing
diffuse proliferative and crescentic GN. IgA
nephropathy.
Membanoproliferative GN
• Clinical Presentation
• Combination of nephritic and nephrotic features,
acute or subacute decline in GF.
• Pathology Findings
• Diffuse proliferation of mesangial cells and
infiltration of glomeruli by macrophages
• Etiologies
• Immune complex GN, In association with
thrombotic microangiophaties, in association with
deposition diseases.
Membanoproliferative GN
• Clinical Presentation
• Combination of nephritic and nephrotic features,
acute or subacute decline in GF.
• Pathology Findings
• Diffuse proliferation of mesangial cells and
infiltration of glomeruli by macrophages
• Etiologies
• Immune complex GN, In association with
thrombotic microangiophaties, in association with
deposition diseases.
Deposition diseases
• Clinical Presentation
• Combination of nephritic and nephrotic features.
Renal failure over months to years.proteinuria,
hematuria and hypertension.
• Pathology Findings
• Mesangial expansion and thinckening of glomerular
capillari wall
• Etiologies
• Amyloid, Cryoglobulinemia, Light chain deposition
disease.
GENRALITIES
G
L
O CLINICOPATHOLOGIC
M
E
R
U PRIMARY MECHANISMS
L
A
R
CORRELATION BETWEEN
I SITE AND PRESENTATION
N
J
U
R CLASIFICATION
Y
Primary Mechanisms of Glomerular Injury
Immunologic
• Defects
• Inmmunoglobulin
• Cell-mediated injury
• Cytokine (or other soluble factor)
• Persistent complement activation
• Glomerular Disease
• Immune complex-mediated GN
• Pauci-immune GN
• Primary focal segmental glomerulosclerosis
• Membranoproliferative GN type II
Inherited
• Defects
• Defect in gene for a 5 chain of type IV collagen
• Abnormally thin basement membrane
• Glomerular Disease
• Alport`s syndrome
• Thin basement membrane disease
CLINICAL PRESENTATIONS
Immune Response
Antibody
IgG, IgA T Cells
Deposit Formation
In situ, complex trapping
Mediation
Complement, Chemokines Cytokines, Vasoactive
Effector Cells
PMNs, macrophages Glomerular cells
FG AZOEMIA
reabsorption
Na and H2O
Tubular
volume OLIGURIA
Extracelular HYPERTENSION
Volume EDEMA
Acute renal failure
CLINICOPATHOLOGIC
Renal failure
• 1/Cr plot
• Linear deterioration
Asymptomatic
Proteinuria 150mg to 3g/day
Hematuria > 2 red blood cells
Perhigh-power field (> 10x106 cells/L
Nephritic syndrome In spun urine (red blood cells
(Inflamasi glomerulus) Usually dysmorphic
Oliguria
Hematuria : red cells casts
Proteinuria; usually < 3g/day Nephrotic syndrome
Oedema Proteinuria; adult > 3,5 g/day
Hypertension Child > 40 mg/h per m2
Abrupt onset Edema
Hypercholesterolemia
Lipidemia
dysmorphic
3 Broad diagnostic categories
• 1) Granular deposits of inmunoglobulin
(immune complex GN)
Asymptomatic
Proteinuria 150mg to 3g per day
Hematuria >2 red blood cells
per high-power field (>10 x 106 cells/L)
in spun urine (red blood cells usually dysmorphic)
Nephritic syndrome
Oliguria
Hematuria : red cell casts
Proteinuria : ussually <3g/day
Edema
Hypertension Rapidly progressive glomerulonephritis
Abrupt onset, usually Renal failure over days/weeks
self-limiting Proteinuria : usually <3g/day
Hematuria : red cell casts
Blood pressure often normal
May have other features of vasculitis
Chronic glomerulonephritis
Hypertension
Renal insufficiency
Proteinuria >3g/day
Shrunken smooth kidneys
Glomerular changes in disease
• Proliferation
• Sclerosis
• Necrosis
• Increase in mesangial
matrix
• Changes to basement
membrane
• Immune deposits
• Diffuse vs focal
• Global vs segmental
Thin membrane disease
• Most common GN
• Microscopic haematuria
• Familial
• Benign
• No treatment needed
• Most young people with
isolated microscopic
haematuria have thin
membrane disease
Mesangial IgA disease
• Usually children
• Nephrotic syndrome with
highly selective
proteinuria and
generalised oedema
• Rarely hypertension or
ARF
• T cell mediated – VPF
• Steroid sensitive usually
• Spectrum of disease to
FSGS
Minimal chance
• Diffuse endocapillary
proliferative GN
• Post infectious; usually
Gp A Strep
• Acute nephritic syndrome
• Uraemia rare
• Self-limited; rarely death
from BP
• Abnormal RUA for up to
2 yrs
• Circulating immune
complex mediated
FSGS
Primer / sekunder (hepatitis A, HIVAN).
Tx CST 1 – 2 mg/ kgBB/ hari (3-4 bulan)
tappering terapi > 6 bulan
Kombinasi dengan CyA menurunkan
relaps.
CyA : 4 – 20 mg/ kgBB /hari hambat
kerusakan glomerulus.
Plasmapheresis
ACEI
AntiGBM disease
• RPGN + Lung
haemorrhage
• Destructive process –
medical emergency!
• Antibody-mediated
• One hit
• High dose
immunosuppression
• Plasma exchange
Tx MN
Tx MCNS
Immunosuppression in GN: Summary
• Oral Prednison
• Cyclophosphamide and Oral Prednison
• Chlorambucil and Methylprednisolon
• Cyclosporin
Response to Steroid
• Remission Complete
• Remission Partial
• Steroid Resistant
Glomeruler Disease
Sign Resolution
• Diuresis 1 week
• Hypertension 2 weeks
• Cr to normal (longest on HD-38 days) 3-4 weeks
• EM Humps 6-7 weeks
• Hematuria 3-6 weeks
• Proteinuria 3 years : 15%; 10 years : 2%
Minimal change 70 15
Focal Sclerosis 10 35 (black = 60)
Membranous 15 33
Membranoproliferative 10 10
Minimal change / Focal Sclerosis
• Etiology : unknown
• Immune response : T cell
• Deposit formation : none
• Mediation : T cell permeability factor (s)
• Response : Effacement, detachment
• Concequences : proteinuria
Clinical Clasification
Asymptomatic
Proteinuria 150mg to 3g per day
Hematuria >2 red blood cells
per high-power field (>10 x 106 cells/L)
in spun urine (red blood cells usually dysmorphic)
Nephritic syndrome
Oliguria
Hematuria : red cell casts
Proteinuria : ussually <3g/day
Edema
Hypertension Rapidly progressive glomerulonephritis
Abrupt onset, usually Renal failure over days/weeks
self-limiting Proteinuria : usually <3g/day
Hematuria : red cell casts
Blood pressure often normal
May have other features of vasculitis
Chronic glomerulonephritis
Hypertension
Renal insufficiency
Proteinuria >3g/day
Shrunken smooth kidneys