Robbins Chapter 20 - The Kidney - Part 2 Flashcards
Destruction of glomeruli/reduction of GFR to 30-50%
ESRD progresses at a steady rate
2 major characteristics of progressive renal damage
Principal injury- Focal segmental glomerulosclerosis
Accompaning injury - Tubulointerstitial fibrosis
FSGS
Progressive fibrosis after injury
Increased proteinuria and impaired function
Initiated by adaptive change: compensatory hypertrophy of healthy areas of kidney
Reduction in renal mass -> HTN and hypertophy -> Epithelial damage -> proteinuria -> mesangial proliferation and macrophage infiltration -> accumulate ECM -> sclerosis
(vicious cycle)
Interrupting glomerulosclerosis process
Renin-angiotensin inhibitors
reduce HTN and inhibit compensatory mechanisms
Tubulointerstitial fibrosis
Tubular damage and interstitial inflammation
Better correlation in decline of renal function
Ischemia downstream, surrounding inflammation, or loss of peritubular capillary network
Proteinuria can directly injure and activate tubular cells
Nephritic syndrome
Inflammation of glomeruli
**Hematuria, red cell casts in urine, azotemia, oliguria, mild to moderate HTN
Proteinuria and edema are common but not as severe
Acute proliferative glomerulonephritis/ Postinfectious Glomerulonephritis
Diffuse proliferation of glomerular cells
Influx of leukocytes
Typically cause by immune complexes
Poststreptococcal Glomerulonephritis
1-4 weeks post group A strep infection with certain M proteins (12, 4 and 1)
Usually children age 6-10
Immune complexes formed in situ
Elevated antibody titers, decreased serum complement, granular immune deposits
SpeB
Principle antigenic determinant for poststrep GN
Poststrep GN Morphology
Enlarged, hypercellular glomeruli
IgG, C3 and IgM deposits in mesangium and GBM - focal and sparse
Subepithelial humps
Subendothelial deposits early on
Poststrep GN Clinical course
Young child with malaise, fever, nausea, oliguria, hematuria (coke colored urine) 1-2 weeks after sore throat
Mild proteinuria, periorbital edema, mild HTN
Adult more atypical with sudden HTN, edema and BUN
95% children recover with minimal therapy
60% adults recover quickly
Small numbers progress to rapid progressive GN
Nonstrep Acute GN
Similar course with staph, pneumonia, meningococcemia, hep B, hep C, HIV, varicella, mono, malaria, toxo
Staph differs by sometimes creating IgA deposits
Rapid progressive GN
No specific etiology Rapid loss of function Severe oliguria and nephritic signs Death in weeks to months Crescents in most glomeruli **Immunologically mediated - 3 types
Type 1 - anti GBM
Linear immune deposits in GBM
Antibodies to portion of collagen IV alpha3 chain
Goodpasture syndrome
Antibodies cross react Pulmonary hemorrhage (recurrent hemoptysis) with renal failure
HLA-DRB1
Associated with type 1 (autoimmunity)
Type 2 - immune complex deposition
Complication of any immune complex nephritides
Postinfectious, SLE, IgA nephropathy, and Henoch-Schonlein purpura
Type 3 - Pauci-immune
Lack of detectable anti-GBM or immune complexes
Circulating antineutrophil cytoplasmia antibodies
May be associated with Wegener granulomatosis but usually idiopathic
**Manifestation of small vessel vasculitis or polyangiitis limited to peritubular capillaries
Wegener granulomatosis
Granulomatosis with polyangiitis
Inflammation of blood vessels restricting blood flow to certain organs
RPGN morphology
Distinctive crescents with prominent fibrin strands
May show ruptures in GBM - allows leukocytes and coagulation material through
RPGN clinical course
Hematuria with blood cell casts, moderate proteinuria, variable HTN and edema
Serum analysis can be helpful (antiGBM, antinuclear, ANCAs)
Culminates in oliguria
Serum exchange may help some early on as well as steroid treatment
Many patients require chronic dialysis
Nephrotic syndrome
Derangement in glomerular capillary walls resulting in increased permeability to plasma proteins
Massive proteinuria (greater than 3.5 gm)
Hypoalbuminemia (less than 3 gm)
General edema
Hyperlipidemia and lipiduria
Vulnerable to infection - loss of immunoglobulins
Thrombotic/thromboembolic complications - loss of anticoagulants -> renal vein thrombosis
Generalized edema
Decreased colloid osmotic pressure or increased hydrostatic pressure (increased sodium and water retention)
Highly selective proteinuria
Mostly low weight proteins (albumin)
Poorly selective proteinuria
Variety of protein loss, low and high weight
Most frequent cause of nephrotic syndrome in under 17 in NA
Lesion primary to the kidney
Most frequent cause of nephrotic syndrome in adults in NA
Systemic disease
Most frequent systemic cause of nephrotic syndrome
Diabetes, amyloidosis, SLE
Most frequent primary lesions causing nephrotic syndrome
Minimal-change disease (children), membranous glomerulopathy (adults) and focal segmental glomerulosclerosis
Less common cause of nephrotic syndrome
Proliferative glomerulonephritides: MPGN and IgA nephropathy
Membranous Nephropathy
Diffuse thickening of glomerular capillary wall due to deposits of Ig on subepithelial side
75% primary
25% secondary/systemic problem
Systemic causes of membranous nephropathy
Drugs (penicilamine, captopril, gold, NSAIDS)
Malignant tumors (lung, colon, melanoma)
SLE (10-15%)
Infections (hep B, hep C, syphilis, schistosomiasis, malaria)
Other autoimmune
Membranous Nephropathy Pathogenesis
Chronic immune complex mediated
Secondary - known antigens
Primary - idopathic, linked to HLA-DQA1, usually antibodies to renal autoantigen (phospholipase A receptor)
C5b-C9 MAC makes capillary leaky
Membranous Nephropathy Morphology
Diffuse thickening of glomerular capillary wall on subepithelial side
Segmental sclerosis may eventually occur
Membranous Nephropathy clinical course
Usually insidious onset of nephrotic syndrome
Proteinuria nonselective
Does not respond well to corticosteroids
Progressive sclerosis leads to increased creatinine and BUN and HTN
10% renal failure, 40% chronic disease
Recurs in 40% who receive transplant for ESRD
Minimal change disease
Relatively benign
Diffuse effacement of foot processes, glomerulus appears normal, no deposits, lipoprotein reabsorption
Peak incidence between age 2 and 6
Some form of immune dysfunction - angiopoietin-like-4
Minimal change disease clinical course
Massive proteinuria, renal function remains ok without hematuria and HTN
Drastically respond to corticosteroids although it may recur and individual may become steroid dependent
Minimal change disease associated with
Hodgkin lymphoma in adults as well as other lymphomas and leukemias NSAID therapy (acute interstitial nephritis)
Most common cause of nephrotic syndrome in adults in US
Focal Segmental Glomerulosclerosis
Focal Segmental Glomerulosclerosis
Sclerosis of some glomeruli and only portion (segment) of capillary tuft is involved
Higher incidence of hematuria, reduced GFR and HTN
Proteinuria more nonselective
Poor response to corticosteroids
50% develop ESRD
Types of FSGS
Primary - idiopathic In association - HIV, heroin use, sickle-cell, obesity Secondary event - scarring Adaptive response to loss of tissue May be inherited
Idiopathic FSGS
10% nephrotic syndrome in children
35% nephrotic syndrome in adults
FSGS Pathogenesis
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