Pathology of Common

GLOMERULAR SYNDROMES
Dr Purushotham krishnappa
Objectives
To learn basic renal terminologies
Understand the common clinical features
of common glomerular diseases
Nephrotic syndrome
Nephritic syndrome
Rapidly progressive glomerulonephritis
Basic terminology and concepts
Azotemia

Biochemical abnormality
Raised blood urea nitrogen and creatinine
Decreased GFR

The cause may be:
Renal
Extrarenal
Pre-renal: hypoperfusion
Post-renal: obstruction

Basic terminology and concepts
Uraemia

Azotaemia plus clinical signs and symptoms
Metabolic
Endocrine
Gastrointestinal uraemic gastroenteritis
Peripheral nerves peripheral neuropathy
Heart uraemic fibrinous pericarditis.
Important terminology
Proteinuria protein in the urine
Haematuria blood in the urine
Clinical syndromes
Clinical syndromes are convenient starting points to
identify and evaluate kidney diseases.

Syndromes related to injury to the glomerular capillary
wall are quite specific for glomerular diseases.

Clinical presentations of diseases of tubules, interstitium
and blood vessels are less specific.
They often present as non-specific acute or chronic
renal insufficiency.

Clinical syndromes

Point to remember:
Some diseases may have more than 1 clinical
presentation with different syndromes or a mixture of
syndromes, e.g. SLE
Therefore, clinical syndromes alone may not be
sufficient.
A renal biopsy - based diagnosis may be required.
Clinical syndromes for
glomerular diseases
1. Nephrotic syndrome
2. Acute nephritis
3. Asymptomatic haematuria
4. Asymptomatic proteinuria.
5. Rapidly progressive glomerulonephritis
6. Acute renal failure
7. Chronic renal failure
Nephrotic Syndrome
1. Heavy proteinuria (Nephrotic range is
more than 3.5 gm /day)
2. Hypoalbuminaemia (less than 3 gm/dl)
3. Severe oedema- generalised
4. Hyperlipidemia

Classic example: minimal change disease
Causes of Nephrotic Syndrome
Primary Glomerular Disease
Membranous glomerulopathy - Adults
Minimal change disease - Children
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritides
Other proliferative glomerulonephritis (focal, "pure mesangial," IgA
nephropathy)
Systemic Diseases
Diabetes mellitus
Amyloidosis
Systemic lupus erythematosus
Drugs (nonsteroidal anti-inflammatory, penicillamine, "street heroin")
Infections (malaria, syphilis, hepatitis B and C, acquired
immunodeficiency syndrome)
Malignant disease (carcinoma, lymphoma)
Miscellaneous (bee-sting allergy, hereditary nephritis)

Causes and conditions associated
with nephrotic syndrome
Frequency:
Children (unselected):
Minimal change disease 88%
Focal segmental glomerulosclerosis 5%
Membranoproliferative glomerulonephritis 1%
Adults:
Minimal change 15%
Focal segmental glomerulosclerosis 35%
Membranous glomerulopathy 33%
Membranoproliferative glomerulonephritis 2%
Nephrotic syndrome
Associated with a myriad of diseases.

A few forms of glomerular diseases
account of most of the cases of nephrotic
syndrome.
Hypoproteinemia
Albumin
Immunoglobulins
Metal binding proteins
Erythropoietin urinary
loss
Transferrin
Complement deficiency
Coagulation components
Hyperlipidemia
Hypercholesterolemia
Hypertriglyceridemia
Low-density lipoproteins (LDL)
Very low- density lipoproteins (VLDL)
Mechanisms of Hyperlipidemia
Increased hepatic synthesis of LDL, VLDL and
lipoprotein (a) in response to hypoalbuminemia


Urinary loss of HDL

Enzymatic changes with abnormal lipid
biosythesis and degradation


Edema
Lower colloid osmotic pressure?

15mmHg H
2
O
colloid osmotic pressure 26 mmHg

Edema
Diagnosis
Diagnosis:
NS?
Primary or secondary?
Complications?




Differential diagnosis
Primary Secondary
children minimal change allergic purpura
nephritis
Teenager mesangial proliferative FSGS
nephritis
Middle age mesengial capillary SLE LN
nephritis
old age membranous myeloma,
amyloidosis
nephropathy

Complications
Acute renal failure( ARF)
Hypoalbuminemia Hypovolemia pre-renal
azotemia

Dyslipidemia
Treatment
Support care
Rest in bed; limitation of protein
intake(0.8-1.0g/kg/d); limitation of salt
intake (<3g/d)

Diuretic therapy

Diminishing proteinuria: ACEI and ARB

Treatment
Minimal changes: sensitive to steroids;
single drug; reuse when relapse;
combined with cytotoxic drugs when
resistant or dependent on steroids
Membranous GN: combine steroid with
cytotoxic drugs or cyclosporin; avoid using
drugs when Scr>354umol/L; for the
patients with risks for progressing,
otherwise, investigate 6 months
(antihypertensive).

Treatment
FSGS: sensitive to steroids in 30-50% of
patients; slow response to therapy;
steroids therapy (onset) for 3-4 months; if
not response until 6 month (resistant),
then try cyclosporine.
Mesangial proliferative GN: no evidence
show that adults will response to steroids;
aspirin

Acute Nephritis

Acute onset
Gross hematuria
Hypertension
Mild to moderate proteinuria





Classic example: acute post-streptococcal
glomerulonephritis
Asymptomatic hematuria or
proteinuria

Haematuria

Subnephrotic proteinuria
Rapidly Progressive
Glomerulonephritis

Characterised by:

Acute nephritis

Proteinuria

Acute renal failure

Classic example: Crescentic glomerulonephritis
Normal Glomerulus PAS
staining basement membrane
Histologic Alteration of
glomerulus - 1
Hypercellularity
(proliferative)
Increase in number of cells
in glomerular tuft.
Due to:
Cellular proliferation of
mesangial or endothelial
cells (endocapillary)
Leukocyte infiltration
Crescent formation
(extracapillary)
Histologic Alteration of
glomerulus - 2
Basement membrane
thickening

Thickening of capillary wall by light
microscopy

On electron microscopy -
deposition of amorphous material
often immune complexes on
endothelial/epithelial side of
basement membrane e.g.
membranous glomerulopathy

OR
Thickening of basement
membrane proper e.g diabetic
glomerulosclerosis
Histologic Alteration of
glomerulus- 3
Hyalinisation or
sclerosis of
glomerulus
Amorphous substance
plasma proteins
Collagen
Capillary lumina
obliterated
End result of various
glomerular damage

Histologic Alteration of
glomerulus

1. Hypercellularity (proliferative)

2. Basement membrane thickening

3. Hyalinisation or sclerosis of
glomerulus


Glomerular Pathology
Terminology

Diffuse - all glomeruli affected

Global - the whole glomerulus affected

Focal only a portion of glomeruli affected

Segmental only a part (segment) of each glomerulus affected

Mesangial mesangium affected.
Summary of Glomerular Syndromes
Acute nephritic syndrome Hematuria, azotemia, variable
proteinuria, oliguria, edema, and
hypertension

Rapidly progressive
glomerulonephritis
Acute nephritis, proteinuria, and
acute renal failure

Nephrotic syndrome >3.5 gm proteinuria,
hypoalbuminemia, hyperlipidemia,
lipiduria
Chronic renal failure Azotemia uremia progressing for
years
Asymptomatic hematuria or
proteinuria
Glomerular hematuria; subnephrotic
proteinuria