Location and Structure

Details of a Glomerulus - The Membrane for

Filtration
Proximal
Tubule

Inside of
the Capillary
- Blood Side -

Bowmans
Capsule

Capillary Wall
- Filter-

Capillary
Loops
Efferent
Arteriole
Detail of the Capillary
Wall

Afferent
Arteriole

Healthy Kidney

Diseased Kidney

Physical Basis

Renal Replacement

Outside of
the Capillary
- Urine Side -

A picture of a normal human glomerulus

against which to compare the various diseases.
Tufts of
of capillaries
capillaries
Tufts
Bowmans Space

Thin
basement membranes

Afferent arteriole

Nuclei of
glomerular cells

Pathological features of glomerulonephritis

Descriptive Terms
Patterns of Damage - 1
One Glomerulus compared with another

All glomeruli normal

= No glomerulonephritis

Some glomeruli abnormal

All glomeruli abnormal

= focal glomerulonephritis = diffuse glomerulonephritis

(often secondary to
systemic disease)

Pathological features of glomerulonephritis

Descriptive Terms
Patterns of Damage - 2
Within a single glomerulus

Damage to part

Damage to all parts

Normal

of glomerulus only

of glomerulus only

= No glomerulonephritis

= segmental
glomerulonephritis

= global
glomerulonephritis

Glomerular Injury
Global vs. Segmental
X
X
X
X

X
X

X
X

X
X
X
X

Global Disease

X
X

Segmental Disease

Nephritic
Syndrome

Definisi:
It is a clinical pattern characterized by sudden onset of :
1.
2.
3.

Edema (sodium and fluid retention)

Hypertension
Urinary changes :
a. Mild proteinuria
b. Variable degree of haematuria (macroscopic or
microscopic, RBCs cast)
c. Olygouria
d. Mild azotemia

Etiology :
1. Immune complex disease :
primary

Idiopathic membranoproliferative MPGN

Mesangioproliferative GN
Bergers disease (Ig A nephropathy)
Membranoproliferative GN

Secondary

Infection : Post streptococcal-Infective endocarditis

Collagenic : SLE
Allergic : Henoch Schonlein Syndrome
Drug : Sulpha

2. Anti glomerular basement membrane Abs :

Good pasture syndrome

3. Pauci Immune : PAN-TTP-DIC

If the inflammatory process is severe, GN
may lead to a greater than 50% loss of
nephron function over the course of weeks
to months such a process is called Rapidly
Progressive GN and maybe associated
with crescent in > 50% of the glomeruli.
This of GN may occur in post infectious,
IgA nephropathy, SLE and others

Clinical Picture of Nephritic

Syndrome :
Symptoms :
1.
2.
3.

anorexia, nausea & vomiting dt mucosal edema

Red urine dt haematuria
Head ache, epistaxis dt hypertension

Sign :
1. Edema : dt salt & H2O retention
acute onset, appear in the eye lid in the morning &
disappear
in the afternoon to appear in the ankle in ambulated patient
Firm, pitting dt hypoproteinemia
Rarely generalized & not associated with serious effusion
2. Hypertension : salt & water retention

3. Urine changes :
oligouria
haematuria (cola colour, smoky or reddish brown urine), micro and
macroscopic
Proteinuria < 2 g/day

Clinical Picture of
Complication:

CP of Complication
1. Circulatory congestion :
Congested pulsating neck vein
Pulmonary edema (dyspnoe or orthopnea) dt hypervolemia
Normal circulation time or heart failure (gallop &
circulation
time)
2. Hypertensive encephalopathy :
dt loss of autoregulation of cerebral blood flow leads to
brain
edema
C/P : Head ache + vomiting + blurring of vision + focal sign
3. Non Resolution :
Rapid progressive GN ARF
Chronic GN CRF
Asymptomatic proteinuria which may reach the nephrotic
range ( 3.5 g/day nephrotic phase of nephritic syndrome

Clinical Picture of the

Etiology

CP of the Etiology
1. Clinical manifestation of Post-Streptococcal GN (PSGN) :
a. Patients presenting with Acute Nephritic Syndrome, often
have evidence of a recent infection of the pharynx or skin
with group A B-haemolytic Streptococci especially type 12
b. Age : Children and adolescence
c. This may occur sporadically or in epidemics
d. It commonly appears after pharyngitis or impetigo within 1-3
weeks after infection (1-2 weeks in pharyngitis & 2-4 weeks
in impetigo)
2. Clinical manifestation of IgA Nephropathy
a. IgA Neph (Bergers disease) is a primary renal diseases of IgA
deposition in the glomerular mesangium proliferative GN
b. It is a common seen in children and young adults
c. Recurrent macroscopic haematuria is the most frequent
clinical presentation

Clinical Picture :

d. It is frequently associated with :

- URTI (follow by haematuria 1-2 days after onset or
URTI)
- Gastrointestinal symptoms or flu like illness
e. Rarely, it presents with microscopic haematuria,
proteinuria &
progressive RF
f. Rapidly Progressive RF is unusual. It may results from
ATN as
consequence of macroscopic haematuria or
superimposed
crescentic nephritis
g. Recurrent IgA deposisition is common after
transplantation

IgA Nephropathy

IgA

Clinical manifestation of Henoch

Schonlein Purpura (HSP)
a. Haematuria
b. Arthritis
c. Abdominal pain
c. Purpura

Henoch Schonlein Purpura

Often a multi-systemic Illness

Wegeners Granulomatosis
Sinusitis
Lung haemorrhage
Skin rash
Arthritis
Testicular involvement
mononeuritis
Any organ

Wegeners Granulomatosis

Cavitating Nodules

Wegeners Granulomatosis

Haemorrage

Wegeners Granulomatosis

Wegeners Granulomatosis
c ANCA associated disease
Microscopic polyarteritis p ANCA assoc
disease
Untreated 80% mortality
Cyclophosphamide and Pred +/- plasma
exchange
Treated 80% cured, 10% resistant disease,
10% die from side effects of the drugs

Systemic Lupus
Erythematosis
Arthritis
Skin rash
Hair loss
Anaemia, thrombocytopenia,
leucopenia
Pleuritis, pericarditis
Eye inflammation
Mouth ulcers

Lupus Nephritis
Auto-immune disease
7:1 female to male
Classical treatment
Cyclophosphamide and prednisolone.
Good recent evidence for
Mycophenolate mofetil
Hardly ever cured usually just get it
under control

Lupus Rash

Lupus Nephritis

Diffuse proliferative GN (grade IV)

Wire loops

Lupus Nephritis
Grade
Grade
GN
Grade
Grade
Grade
Grade

I
II

Normal
mesangial proliferative

III
IV
V
VI

focal proliferative GN
Diffuse Proliferative GN
Membranous GN
diffuse scarring

Goodpastures

IgG and C3

Goodpastures
Autoantibody directed against the
basement membrane of the Glomerulus
and Alveolus
Pulmonary Haemorrhage and
Crescenteric acute renal failure
Plasma exchange, steroids and
cyclophosphamide
Rare to recover renal function. Can
usually save their lives

Investigations :
A. Urine analysis :
Physical

Microscopic or gross haematuria (smoky)

Turbid (proteinuria)
Oligouria
specific gravity

Biochemical : proteinuria < 3 g/day

Microscopic :

Dismorphic (deformed) RBCs (Glomerular origin)

Hyaline & tubular epithelial casts
RBCs cast (Diagnostic)
Granular casts

Investigations :
B. Blood Chemistry :
Anaemia
Creatinine is usually normal
BUN maybe increased disproportionately
Serum albumin is often (dilutional + urinary
loss)
Na dilutional due to volume overload
Hypercholesterolemic acidosis with mild K
C. Renal Imaging : US : Mild swelling of kidneys or
Normal

Investigations : (cont)

D. Renal Biopsy :
Indicated if there is atypical presentation or there is
severe azotemia or anuria or persistenly low C3 or
persistent proteinuria > 6 months
Light microscopy :

Show diffuse proliferative GN (mesangial cell proliferation,

infiltration with PMN, monocyte in capillary lumina,
mesangium). Severe disease may show crescent in urinary
space.

Electron microscopy :

Show large dense sub epithelial deposits or humps

Immunofluorescence (IF) :

Show IgG and C3 in a granular pattern in the mesangium and

along the capillary basement membrane

Investigations : (cont)

D. Serological test :

In PSGN
1. serum complement (CH50, C3). C3 returns to normal level
within 6-8 weeks of the disease. Persistently low C3 suggest
MPGN, lupus or endocarditis
2. Anti Streptolysin O titers (ASOT) unless antibiotic treatment
was
taken. It starts to rise 10 14 days after pharyngeal infection,
peaks at 3-4 weeks then declines maybe till 6 months
3. Throat or skin culture for Group A Stretococcus
In Ig A nephropathy :
1. Serum Ig A level is increased up to 50% of patients
2. Serum complement level are usually normal

Nephrotic
> 3g proteinuria
Oedema
Low serum
Albumin
Hypercholesterol
bacterial infections
increased clotting

Nephritic

Blood and proteinuria

Red cell casts
Hypertension
Raised creatinine

Often systemic illness

Treatment :
Treatment of the disease :
General treatment
Complete bed rest, till edema, haematuria &
hypertension subside
Diet : High CHO diet
Salt & H2O restriction (in marked
oliguria and
edema)
Protein restriction (in case of renal
failure)
K restriction (in case of Hyperkalemia)

 Treatment of the disease :

Symptomatic treatment
Diuretic (Furosemide) for edema
Nifedipine, furosemide or ACE-I for hypertension
In the vast majority of patient < 1 g/day, no specific
treatment is provided
In patient with significant proteinuria > 1 g/day, ACE-I
or ARB should be used to reduce proteinuria. The
target BP is < 130/80 mmHg
Patients with progressive disease with deteriorating
kidney functions aggressive treatment including
steroid, plasmaparesis or cytotoxic drugs
Renal transplantation is an option for patients with
ESRD

 Treatment of the disease :

Treatment of the cause :
A. Post Streptococcal GN
Penicillin 1 million Unit/ 6 hours IV for

1 week

B. Good Pasture Syndrome :

- Plasmapharesis
- Pulse Corticosteroid therapy
1 g methyl prednisolone
maintenance : 2 mg/kg/ every other day
- Mini-pulse corticosteroid therapy : 250 mg prednisolone/day
for 3
days (less toxic)
C. SLE
- Pulse corticosteroid therapy
- Cyclophosphamide pulse therapy
- Plasmapharesis

Treatment of the
complication:
Heart failure :

Salt restriction
Diuretic
Small dose digitalis
Peritoneal dialysis

Renal Failure :
Dialysis

Hypertensive encephalopathy :
Mannitol for brain edema
Diazepam for convultion

Prognosis:
Prognosis in children is very favourable
Adult are more prone to crescentic
formation and chronic Renal Insufficiency
Less than 5% of adults will develop a
RPGN and smaller percentage will
progress to ESRD
Patients with proteinuria < 1 g/24 h
usually have good prognosis