Glomerular Diseases Flashcards
What are some examples of primary glomerular disease
oMinimal change glomerular disease
oMembranous glomerulonephritis
oIgA nephropathy
oAcute diffuse proliferative glomerulonephritis
What are some common causes of secondary glomerular nephritis
Common
oSLE
oPolyarteritis nodosa
oDiabetes mellitus
oAmyloidosis
oMalarial nephropathy
What are some uncommon causes of secondary glomerular nephritis
oSarcoidosis
oRheumatoid arthritis
oHemolytic uremic syndrome
oAIDS nephropathy
What is the pathogenesis of secondary glomerular nephritis
Circulating immune complex deposition:
oAntigen + Antibody - deposition in glomeruli - binding with complement – inflammation - glomerular injury.
oAntigen may be exogenous or endogenous
- 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
Give some examples of the glomerulopathies
oNephrotic Syndrome
oNephritic Syndrome
oRapidly Progressive Glomerulonephritis
What is the clinical complex of nephrotic syndrome characterized by
oHeavy proteinuria (3.5g/day)
oHypoalbuminemia
oEdema
oHyperlipidemia
oHyperlipiduria
How does proteinuria occur in nephrotic syndrome
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
How does generalized edema come about in nephrotic syndrome
o Hypoalbuminemia - result decrease colloid osmotic pressure
How does hyperlipidemia come about in nephrotic syndrome
oHypoalbuminemia triggers increase synthesis of all form of plasma protein including lipoprotein - hyperlipidaemia
How is hyperlipoproteinemia caused in nephrotic syndrome
o Hyperlipoproteinemia - increase permeability results in hyperlipiduria
How is nephrotic syndrome caused
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
What are some clinical features of nephrotic syndrome
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
What are investigations to make in nephrotic syndrome
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
What are some complications for nephrotic syndrome
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
What is the management for nephrotic syndrome
oDiet
oDiuretics
oHypercholesterolemia
oHypercoagulability
oOliguric renal failure
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
Membranous glomerulonephritis
What are the primary causes for membranous glomerulonephritis (MG)
Primary causes: 85% membranous nephropathy caused by autoantibodies that cross-react with antigens expressed by podocytes.
What are the secondary causes of MG
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)
What is the pathogenesis of a MG
Membranous glomerulonephritis is a form of chronic immune complex nephritis
How is MG seen under a light and electron microscope
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
What are the clinical features a membranous GN
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
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
Nephritic syndrome
What are the types of rapidly progressing glomerular glomerular nephritis (RPGN)
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
What are the clinical features of RPGN
Like nephritic syndrome
But more marked oliguria and azotemia
90% patient required dialysis and transplantation
