glomerulonephritis Flashcards
Define glomerulonephritis
A group of diseases associated with inflammatory injury of the glomeruli indicated by Infiltration of leukocytes, Deposition of immune proteins and Disturbed function of the affected tissue
Which cell types can be involved in glomerulonephritis
Mesangium, podocytes, capillaries/endothelium, parietal epithelial cells
Nephritic syndrome definition
- Reduction in GFR (an elevated serum creatinine)
- Active urine sediment (RBC’s, WBC’s, and RBC casts)
- Proteinuria (usually sub-nephrotic)
- Edema
- Hypertension
- Reduction in GFR (an elevated serum creatinine)
- Active urine sediment (RBC’s, WBC’s, and RBC casts)
- Proteinuria (usually sub-nephrotic)
- Edema
- Hypertension
- Reduction in GFR (an elevated serum creatinine)
- Active urine sediment (RBC’s, WBC’s, and RBC casts)
- Proteinuria (usually sub-nephrotic)
- Edema
- Hypertension
What causes proteinuria in nephritic syndrome
direct damage to the glomerular capillary wall induced by immunologic mechanisms leading to an increase in protein filtration. <3g/day b/c damage is focal (as opposed to nephrotic syndrome where entire capillary is affected)
What causes reduced GFR in nephritic syndrome
acute, inflammatory process within the glomerulus resulting in glomerular vasoconstriction and/or occlusion or thrombosis of some glomerular capillary loops
What causes active urine sediment in nephritic syndrome
The excretion of red cells, white cells and red cell casts reflects glomerular inflammation and disruption of the GBM
What causes hypertension in nephritic syndrome
consequence of salt and water retention.
What causes edema in nephritic syndrome
increase in tubular reabsorption of salt and water due to reduced, glomerular perfusion with well preserved tubular function leading to expansion of extracellular fluid volume
Does glomerulonephritis require a kidney biopsy for diagnosis?
YES
Syndromes associated with aggressive disease
Rapidly progressive glomerulonephritis (RPGN), Crescentic glomerulonephritis, Pulmonary-Renal syndrome
Rapidly Progressive Glomerulonephritis (RPGN) description, associations and therapy
Serum creatinine doubles or GFR falls by 50% within a few days to 3 months. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
Serum creatinine doubles or GFR falls by 50% within a few days to 3 months. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
Serum creatinine doubles or GFR falls by 50% within a few days to 3 months. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
Crescentic Glomerulonephritis description, associations and therapy
Crescents seen on biopsy. Caused by rupture of capillary wall. Usually associated with Anti-GBM disease, ANCA associated vasculitis and Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
Pulmonary-renal syndrome description, associations and therapy
Glomerulonephritis with pulmonary capillaritis. Presents with nephritic syndrome and hemoptysis. Associated with Anti-GBM disease, ANCA associated vasculitis, Lupus. Therapy is aggressive: cytotoxic drugs and plasma exchange
List mechanisms for glomerulonephritis pathophysiology and associated diseases
1) Deposited immune-complexes: Lupus, MPGN 2) Antibodies specific for renal antigens: Anti-GBM disease, lupus? 3) Other causes of inflammation within glomeruli: Vasculitis (ANCA associated disease), Hemolytic uremic syndrome, C3 glomerulopathy
Describe locations of immune complex deposition within glomeruli
Mesangial, subendothelial, subepithelial, intra-membranous
Describe causes of immune complex formation
Antibodies to glomerular antigens, Antibodies to extra-glomerular antigens (Infections, Cancer, Drugs, foreign substances), Idiopathic (i.e. antibodies to unknown antigens)
How do immune complexes cause damage to glomerulus?
Complement is activated which activates PMNs that release proteases/oxidants causing capillary wall damage, which then leads to fibrin and crescent development. Also, macrophages can be directly activated by deposits.
Drugs used to treat glomerulonephritis
Immunosuppresives: Prednisone, cyclophosphamide, rituximab, IVIg
Which diseases is plasma exchange used and what does it do
Removes large plasma proteins such as auto-antibodies. Used in anti-GBM disease, severe ANCA associated vasculitis, and severe cryoglobulinemia
Post infectious glomerulonephritis etiology, pathology,
Abs + streptococcal Ags lodge in glomeruli and activate complement. Light microscopy: proliferative and exudative glomerulonephritis with infiltration of neutrophils and monocytes. Immunofluorescence (IF): granular deposits of IgG and C3 in the subendothelial, mesangial and subepithelial locations. EM: subendothelial and mesangial deposits, as well as the classic “subepithelial humps”.
Post infectious glomerulonephritis presentation, diagnosis, treatment
Edema, weight gain, hematuria, subnephrotic proteinuria, GFR decreased, severe hypertension. Elevated anti-streptolysin O, decreased C3. Usually get better without treatment
IgA nephropathy description/ presentation, associations, timeline and treatment
Mesangial IgA and mesangial expansion. Usually presents with hematuria +/- subnephrotic proteinuria. Associated with aberrant glycosylation of IgA1. Slowly progressive. Treated with prednisone, BP meds and ACEI
Mesangial IgA and mesangial expansion. Usually presents with hematuria +/- subnephrotic proteinuria. Associated with aberrant glycosylation of IgA1. Slowly progressive. Treated with prednisone, BP meds and ACEI
MPGN
Mesangial proliferation and thickening of GBM. C3 and IgG deposits in capillary walls and mesangium. Presents as nephritic syndrome, with hypertension. Many have Hep C. Poor prognosis.
Lupus nephritis causes
immune complex deposits: Mesangium (hematuria), subendothelial (nephritic syndrome and hematuria), and/or subepithelial (nephrotic)
Classifications of lupus nephritis
I-II: mesangial. III-IV: subendothelial. V: subepithelial. VI: scarring of >90% of glomeruli leading to renal failure.
lupus nephritis pathology and presentation
Immunofluorescence may demonstrate C3, IgG, IgM, IgA, and C1q all within the same kidney. These deposits appear as “lumps and bumps” Can present as nephritic or nephrotic
Anti-glomerular basement membrane disease causes and result
Caused by auto-antibodies to the NC1 domain of the alpha-3 chain of type IV collagen. Can be renal or pulmonary-renal. Often causes crescentic, necrotizing glomerulonephritis and RPGN
Goodpastures triad
pulmonary hemorrhage, iron deficiency anemia and GN associated with circulating antibody to GBM
Anti-glomerular basement membrane disease diagnosis and treatment
Check patients with nephritic syndrome, RPGN, or pulm-renal syndrome. Diagnosed by biopsy(linear IgG deposits) and detection of anti-GBM antibodies. Can see crescent formation. If untreated, progresses to end stage renal disease. Treated with cytotoxic drugs, corticosteroids and plasma exchange
ANCA associated vasculitis diagnosis
Check patients with nephritic syndrome, RPGN, or pulm-renal syndrome. Diagnosed by detection of ANCA (anti-neutrophil cytoplasmic antibodies) and biopsy
ANCA associated vasculitis disease examples, clinical findings and type of ANCA
Granulomatosis with polyangiitis (formerly called Wegener’s disease) causes nephritic syndrome with airway involvement- C-ANCA. Microscopic polyangiitis causes nephritic syndrome with airway involvement- P-ANCA. Eosinophilic granulomatosis with polyangiitis causes lung and skin vasculitis, asthma and eosinophilia- P-ANCA/C_ANCA. Renal limited vasculitis is P-ANCA
Granulomatosis with polyangiitis (formerly called Wegener’s disease) causes nephritic syndrome with airway involvement- C-ANCA. Microscopic polyangiitis causes nephritic syndrome with airway involvement- P-ANCA. Eosinophilic granulomatosis with polyangiitis causes lung and skin vasculitis, asthma and eosinophilia- P-ANCA/C_ANCA. Renal limited vasculitis is P-ANCA
Treatment of ANCA associated vasculitis
High mortality w/out treatment. Cytotoxic drugs, corticosteroids, Rituximab, plasma exchange
Cryoglobulinemia description, pathology, presentation
Cryoglobulins are antibodies that precipitate in the cold. In vivo they can form immune-complexes that precipitate in small vessels, causing vasculitis. Membrano-proliferative pattern of injury with subendothelial immune deposits. Associated with Hepatitis C and presents with proteinuria, hematuria, purpura
Henoch-Schonlein purpura description
in kids: (palpable purpura), arthritis, GI involvement (colic and bleeding) and glomerulonephritis. In adults: renal more severe, systemic less obvious. focal proliferative necrotizing glomerulonephritis, often with crescent formation, accompanied by mesangial and capillary wall deposits of IgA. Similar to IgA nephropathy
