Acute Glomerulonephritis

Soumya Ranjan Parida Basic B.Sc. Nursing 4th year Sum Nursing College

Efferent arteriol

Distal tubule

Endothelial cell

Mesangial cell

Mesangial matrix

Viscaral epithelial cell

Proximal; tubule

Lamina densa

Parietal epitheal cell

Afferent arteriol

Bowman’s capsule

Bowman’s space

GLOMERULUS

Pathogenesis of glomerular diseases

Genetic – • Mutations in exons of DNA• Mutations in the regulatory genes controlling DNA transcription• Abnormal post transcriptional modification of RNA transcripts• Abnormal post translational modifications of proteins

Immunological injury – • AG – Ab – Glomerulus – complement activation – chemtactic and

anaphylatoxin-like factors

Coaglation system activation – • Direct or indirect• Activation of kinin system- chemtactic and anaphylatoxin-like factors

Pathology• Proliferation of glomerular cells –

Generalized – all glomeruli

Focal – some glomeruli

Diffuse – all parts of glomeruli

Segmental – some parts of glomeruli

Endothelial, mesangial cells, mesangial matrix proliferation

Increased glomerular size – norrow the lumens of glomerular

capillaries – renal insufficiency

• Crescent formation in bowman capsule –

Proliferation of parietal epithelial cells

Composition – Fibrin, epithelial cells, BM-like material

macrophages

Fibroepithelial crescent – invasion of connective tissue

Crescent – glomerular cell death – eosinophilic appearance

• Exudation of blood cells –

Neutrophils, eosinophils, basophils, mononuclear cells

• Increase in the width of the BM

• Tubulo interstitial fibrosis –

Injury to the renal tubules – MNC infiltration – soluble factors –

fibrosis – destruction of renal tubules and peritubular capillaries

Pathology

Acute poststreptococcal GN

It is characterized by sudden onset of gross hematuria, edema, hypertension and renal insufficiency

Etiology and epidemiology – • Nephritogenic strains of group-A β hemolytic streptococci –

• Throat serotype – 1,3, 4, 12,25 • Skin serotype – 2, 49, 55, 57, 60 • • Pharyngitis - ( cold weather )• Pyoderma - (warm weather )

Pathogenesis & Pathology

Pathogenesis – Immune complex mediated injury Alternate pathway activation

Pathology - • Light microscopy – All glomeruli enlarged, Bloodless Mesanchymal cell proliferation Mesanchymal matrix proliferation PMN cell infiltration Crescent formation• Immunofluorescence microscopy – Lumpy-bumpy deposits of Ig and complements in BM & mesangium• Electrone microscopy – Electrone dense deposits or ‘humps’ on epithelial side of BM

Clinical manifestations

• Age – 5-12 yrs, uncommon before 3 yrs• Pharyngitis – 1-2 wks• Pyoderma – 3-6 wks• Asymptomatic microscopic hematuria, normal RFT to

ARF• Edema, HT, oliguria, encephalopathy, CHF,nephrotic

syndrome(10 20%)

• Malaise, lethargy, abdominal pain, fever, acute subglottic edema, air way obstruction

• Acute phase – 6-8 wks• Proteinuria and HT – 4-6 wks• Microscopic hematuria – 1-2 yrs

Diagnosis

Normal urine examination -

No cast,except hyaline 1/hpf

RBC – 1-2/hpf

WBC – Male – 0-3/hpf

Female -0-5/ hpf

Epithelial cell few

Bacteria – no organism/oif : unspun

<20/hpf : spun

Urine in AGN –

RBC,

RBC cast,

proteinuria,

PMN cells

Diagnosis

Blood –

Normochromic anemia

C3 level decreased

ASLO – throat infections

2-5 yrs – 120-160 todds unit

6-9 yrs – 240 todds unit

10-12 – 320 todds unit

> 13 yrs - 320 todds unit

DNase B – skin infection

Positive throat culture

Diagnosis

Streptozyme test –

( SLO, DNase B, Hyaluronidase, Streptokinase, NADase )

Renal biopsy –

- ARF

- Nephrotic syndrome

- Absence of evidence of streptococcal infection

- Normal complement level

- Hematuria, proteinuria and low C3 >2 months

Complications

• Hypertension• Encephalopathy• CHF• Hyperkalemia• Hyperphosphatemia• Hypocalcemeia• Acidosis • Seizures• Uremia

Treatment & Prognosis

Treatment –

Diet – Protein, sodium, potassium restricted

Penicillin – 10 days

Fluid restriction

Diuretic

Antihypertensive – CCB, Vasodilators, ACE inhibitors

Prognosis –

95% complete recovery

Recurrences are extremely rare

Membranous Glomerulonephritis

Etiology –

SLE, chronic ITP, neuroblastoma, gonadoblastoma,

syphilis,HBV infection, gold .penicillamine.

Pathology –

LMC – Diffuse thickening of GBM without significant proliferative

changes.

Deposition of membrane-like material by visceral epithelial

cells

Resembles ‘spikes’ on epithelial side of GBM.

IFM – Granular deposits of IgG & C3 on epithelial side.

EMC – Linear staining of IgG,IgA,C3 on tubular BM

Clinical features –

Most common in 2nd decade, nephrotic syndrome (2-6%),

microscopic or gross hematuria, HT (20%).

Diagnosis –

C3 normal except SLE.

Kidney biopsy –

Nephrotic syndrome > 10yrs, Unexplained hematuria and

proteinuria, increased risk of RVT.

Treatment –

Salt restriction, diuretic, prednisone+cyclophosphamide or

chlorombucil

Prognosis –

CRF (20%), Active disease (40%)

Membranous Glomerulonephritis

Pathogenesis – C3 nephritic factors- activates alternative complement pathwayPathology – Type 1 – LMC - most common - Accentuation of lobular pattern - Generalized increased in mesangial cells & matrix - GBM splitting from interposition of mesangial cytoplasm & matrix b/w - endothelial cell and GBM - Formation of crescent IFMC – C3 & lesser amount of Ig in mesangium and along the peripheral capillary in a lobular pattern EMC – immune complex-like deposits in mesangial and subendothelial regionsType 2 – -less common, irregular ribbon-like thickening of GBM, crescent common, splitting rare.

Membranoproliferative (mesangiocapillary) Glomerulonephritis (MPGN)

Type 3 –

Similar to type 1 in LMC & IFMC

EMC – subepithelial and subendothelial

Clinical features –

Most common in 3rd decade, nephrotic syndrome, acute

nephritic syndrome, RFT-normal to decreased, HT.

Diagnosis –

C3 decreased

Renal biopsy – Nephrotic syndrome >10yrs, significant proteinuria

with microscopic hematuria, decreased C3 >8wks.

Treatment –

Long term prednisone EOD

Prognosis –

ESRD (50%), type 2 worst prognosis, recurrent MPGN in kidney

transplant, type 1(13%), type 2(90%)

Membranoproliferative (mesangiocapillary) Glomerulonephritis (MPGN)

SLE Nephritis

Immune complex mediated injury, both T cell and B cell function alteration

WHO classification –

Type 1 – No abnormality

Type 2 – Mesangial lupus nephritis

2a – mild deposit

2b – moderate deposit

Type 3 – FSGN, subendothelial & mesangeal deposits,

necrosis,crescent, sclerosis.

Type 4 – Most common, most severe, diffuse proliferative lupus

nephritis, subendothelial & mesangeal deposits, ‘wire loop

lesions’ necrosis,crescent, sclerosis.

Type 5 – Membranuous lupus nephritis, least common, resembles

membranuous GN except mild to moderate mesangial

proliferation, decreased C3 level.

Clinical features – • Adolescence , female• All type 2 and some type 3 – hematuria, normal RFT, proteinuria <1g/day.

• Some type 3 and all type 4 - hematuria, decreased RFT, proteinuria, nephrotic syndrome, ARF

• Type 5 – nephrotic syndrome.

Diagnosis –

ANA, antibody to double stranded DNA, C3-C4 level decreased.

Treatment – • All patients – prednisone 4-6 months• Type 3 & 4 – 6 monthly IV cyclophosphamide 500-1000mg/m2 followed by

every 3 monthly dosing for 18-36 months.

• Type 1 & 2 – azathioprine single dose daily, 1.5-2mg/kg/day

Prognosis –

Highest risk of progression in type 4

SLE Nephritis

Henoch-schonlein purpura nephritis

Pathology and pathogenesis – • Immune complexes containing IgA1 deposition within the capillaries of the

skin, intestine and glomerulus.• Crescent formation more common and extensive

Clinical manifestations – • 1-3 wks after URI• Gross hematuria (20-30%),• Isolated microscopic hematuria• Hematuria and proteinuria

• Acute nephritic syndrome• Nephrotic syndrome• Renal insufficiency• Ureteritis

Prognosis –

Best - Isolated microscopic hematuria

Poor - Acute nephritic syndrome, Nephrotic syndrome

Rapidly Progressive (crescentic) GN Classification –

1. Immune comlex mediated GN – PSGN, MPGN, lupus, HSP and IgA nephritis.

2. Anti-GBM mediated GN – Goodpasture disease.

3. ANCA mediated GN –Microscopic PAN, Wegner granulomatosis.

Crescent formation.Goodpasture disease – -Pulmonary hemorrage and GN with antibody against type 4 collagen of alveolar BM and GBM. -Continuous linear pattern of IgG along the GBM. Diagnosis –

ANA, Normal C3, anti DNase B,

ANCA to MPO or proteinase-3

Treatment -

According to cause

THANKS