Glomerular Diseases

Question 1

What are some examples of primary glomerular disease

Answer 1

oMinimal change glomerular disease
oMembranous glomerulonephritis
oIgA nephropathy
oAcute diffuse proliferative glomerulonephritis

Question 2

What are some common causes of secondary glomerular nephritis

Answer 2

Common
oSLE
oPolyarteritis nodosa
oDiabetes mellitus
oAmyloidosis
oMalarial nephropathy

Question 3

What are some uncommon causes of secondary glomerular nephritis

Answer 3

oSarcoidosis
oRheumatoid arthritis
oHemolytic uremic syndrome
oAIDS nephropathy

Question 4

What is the pathogenesis of secondary glomerular nephritis

Answer 4

Circulating immune complex deposition:
oAntigen + Antibody - deposition in glomeruli - binding with complement – inflammation - glomerular injury.
oAntigen may be exogenous or endogenous

2. Antibodies directed against antigen on glomerular capillary membrane
   oAnti-GBM antibody disease - antigen fixed in the GBM e.g. good pasture syndrome
   oAntibodies against non GBM antigen

Question 5

Give some examples of the glomerulopathies

Answer 5

oNephrotic Syndrome
oNephritic Syndrome
oRapidly Progressive Glomerulonephritis

Question 6

What is the clinical complex of nephrotic syndrome characterized by

Answer 6

oHeavy proteinuria (3.5g/day)
oHypoalbuminemia
oEdema
oHyperlipidemia
oHyperlipiduria

Question 7

How does proteinuria occur in nephrotic syndrome

Answer 7

oDaily loss of protein 3.5gm or more of protein
oInjury to the capillary wall of the glomeruli result - increase permeability to the plasma protein - allow to - escape from plasma

Question 8

How does generalized edema come about in nephrotic syndrome

Answer 8

o Hypoalbuminemia - result decrease colloid osmotic pressure

Question 9

How does hyperlipidemia come about in nephrotic syndrome

Answer 9

oHypoalbuminemia triggers increase synthesis of all form of plasma protein including lipoprotein - hyperlipidaemia

Question 10

How is hyperlipoproteinemia caused in nephrotic syndrome

Answer 10

o Hyperlipoproteinemia - increase permeability results in hyperlipiduria

Question 11

How is nephrotic syndrome caused

Answer 11

Primary glomerular disease:
oMinimal change nephropathy
oFocal segmental glomerulosclerosis
oMembranous GN

Secondary GN associated with systemic disease:
oDiabetic nephropathy
oAmyloidosis
oDrugs: penicillamine, gold, mercury, cadmium
oAllergic reaction

Question 12

What are some clinical features of nephrotic syndrome

Answer 12

Edema:
oUpper and lower limb
oChildren more obvious on the face
oIntense edema of scrotum or vulva may occur
oBilateral hydrothorax
oEdema of intestine causes anorexia, diarrhea and vomiting

Malnutrition:
oMalnutrition may be due to proteinuria, frequent infection and muscle wasting

Hypercoagulability:
oHypercoagulability manifest as peripheral arterial or venous thrombosis renal vein thrombosis an pulmonary embolism

Question 13

What are investigations to make in nephrotic syndrome

Answer 13

oUrine D/R - Proteinuria
o24 hr. urinary protein - >3g/day
oSerum albumin - less than 3g/dL and total serum protein <6g/dL
oLow-density lipoprotein is elevated but HDL is usually normal
oRaised ESR due to increase serum fibrinogen
oBlood sugar for diabetes and antinuclear factor for SLE
oSerology and renal biopsy

Question 14

What are some complications for nephrotic syndrome

Answer 14

oProtein malnutrition
oHypercoagulability - due to rise in many clotting factors
oImpaired resistance to infection
oSepsis, blood loss and hypovolemia may lead to acute oliguric renal failure

Question 15

What is the management for nephrotic syndrome

Answer 15

oDiet
oDiuretics
oHypercholesterolemia
oHypercoagulability
oOliguric renal failure

Question 16

oSlowly progressive disease
oMost common between 30 to 50 years
oCharacterized by diffuse thickening of GBM
oCause by deposition of immune complex in the epithelial side of the GBM
What condition could this be

Answer 16

Membranous glomerulonephritis

Question 17

What are the primary causes for membranous glomerulonephritis (MG)

Answer 17

Primary causes: 85% membranous nephropathy caused by autoantibodies that cross-react with antigens expressed by podocytes.

Question 18

What are the secondary causes of MG

Answer 18

oInfections (chronic hepatitis B, syphilis, malaria)
oMalignant tumors, particularly carcinoma of the lung and colon and melanoma
oSystemic lupus erythematosus and other autoimmune conditions
oExposure to inorganic salts (gold, mercury)
oDrugs (penicillamine, captopril, non steroidal anti-inflammatory agents)

Question 19

What is the pathogenesis of a MG

Answer 19

Membranous glomerulonephritis is a form of chronic immune complex nephritis

Question 20

How is MG seen under a light and electron microscope

Answer 20

Features of light microscope
oDiffuse thickening of glomerular basement membrane

Features of electron microscope
oApparent thickening of GBM is caused by subepithelial deposits that are separated from each other by small spike in GBM matrix

Question 21

What are the clinical features a membranous GN

Answer 21

o Insidious development of nephrotic syndrome
o In contrast to minimal change disease, the proteinuria is non selective (albumin and globulin both are excreted)
o Usually does not response to corticosteroid therapy
o About 40% lead to renal failure after 2-20 years
o 60% although proteinuria persists, yet they do not progress to renal failure

Question 22

o Inflammatory process causing renal dysfunction
o Over days to weeks, that may or may not resolve
o More than 50% loss of nephron function

oHematuria with RBC casts
oProteinuria (usually non nephrotic range)
oHypertension
oEdema
oOliguria
oUremia

What condition could this be

Answer 22

Nephritic syndrome

Question 23

What are the types of rapidly progressing glomerular glomerular nephritis (RPGN)

Answer 23

Type I RPGN
o Anti-GBM disease
o Characterized by deposition of IgG and C3 on GBM
o Anti-GBM antibodies cross react with the pulmonary alveolar basement membrane - to produce clinical picture of pulmonary hemorrhage along with renal hemorrhage - good pasture syndrome

Characterized by lack of anti GBM antibodies or immune complex by immunofluorescent and electron microscope.
o In serum antineutrophilic cytoplasmic antibody
o Associated with some systemic vasculitis

Type II RPGN (immune-complex mediated disease)
o Complication of any of immune complex nephritis such as post streptococcal GN, SLE, IgA nephropathy, etc.

Type III RPGN
o Characterized by lack of anti GBM antibodies or immune complex by immunofluorescent and electron microscope.
o In serum antineutrophilic cytoplasmic antibody
o Associated with some systemic vasculitis

Question 24

What are the clinical features of RPGN

Answer 24

Like nephritic syndrome
But more marked oliguria and azotemia
90% patient required dialysis and transplantation

Question 25

Like nephritic syndrome
But more marked oliguria and azotemia
90% patient required dialysis and transplantation
What condition might this be

Answer 25

RPGN

Question 26

How is a glomerular disease with a nephritis presentation investigated

Answer 26

Urinalysis
o Dysmorphic red cell
o Red cell cast
o Proteinuria

Serum chemistries
Renal biopsy

Question 27

How is a glomerular disease with disease presentation treated

Answer 27

o Reduction of hypertension
o Salt water restriction
o Diuretics